Theory and applications of ion-selective electrodes Part III

This review of ion-selective electrodes is arranged in the same way as Parts I and II. The continuous growth of the whole subject should be noted. Theory has particularly progressed through mechanistic studies. Among new types of electrodes, ISFET systems have become important. Among new applications of both solid and liquid membrane electrodes, the fluoride electrode still predominates, closely followed by potassium electrodes. In the field of biological and medical applications, the steady growth is significant. More than 800 papers published between mid-1976 and the end of 1978 are mentioned in the review.     

Synthesis of bridgedhead azolo[3,2-a]pyrimidines and imidazo[2,1-b]thiazines through ring transformation of 2H-pyran-2-ones

Suitably functionalized 3-carbomethoxy/cyano-2H-pyran-2-ones are excellent synthons for the synthesis of arenes and heteroarenes of therapeutic importance. The compounds 6-aryl-3-cyano-4-methylsulfanyl-2H-pyran-2-ones have been transformed into bridgedhead azolopyrimidines and imidazothiazines through thermal and base-induced ring transformation reactions with aminoazoles and imidazolidin-2-thiones, respectively.     

Solid-State NMR Study of Phase Separation and Order of Water Molecules and Silanol Groups in Polysiloxane Networks

Homogeneity and structure of organically modified polysiloxane networks prepared by sol-gel co-condensation, as well as location and nature of water molecules and silanol groups were studied by 1D and 2D solid-state NMR. ¹H–²⁹Si and ¹H–¹H interatomic distances were estimated from variable contact-time CP/MAS experiments, ¹H NMR chemical shifts and off-resonance WISE NMR. A structure model of these networks is proposed and discussed. The fraction of proton-inaccessible units Q⁴ in the networks decreases with increasing amounts of dimethylsiloxane (D) and methylsiloxane (T) units. In contrast to systems prepared by co-condensation of tetraethoxysilane (TEOS) with dimethyl(diethoxy)silane (DMDEOS), proton-inaccessible units form essential fraction in networks prepared by co-condensation of TEOS with methyl(triethoxy)silane (MTEOS). The proton-accessible part of the networks with high O/Si ratios is nano-heterogeneous phase, which is composed of water containing Q ⁱ particles separated by copolymer domains. The overall homogeneity and uniformity of binding sites around silanol groups increases by co-condensation TEOS with DMDEOS or MTEOS, while the amount of physisorbed water as well as the hydrogen bond strength decreases, as compared with neat silica gel prepared by polycondensation of TEOS.     

Transient absorption and laser output of YAG : Nd

YAG : Nd grown under 98% Ar 2% H₂ protective atmosphere free of nitrogen or hydrocarbons showed after UV irradiation broad absorption peaked at 1·9×10⁴ cm^–1 which disappeared relatively slowly at room temperature. It was more intensive in oxygen treated samples than in those annealed in hydrogsn. Transient absorption suppresses laser output by the increase of absorption at 0·94×10⁴ cm^–1 (1064 nm) and, particularly in CW mode, by the anomalous rod deformation. YAG : Nd containing Fe ions (2·10^–4 wt%) showed no transient absorption.     

Rutin Inhibits Ox-LDL-Mediated Macrophage Inflammation and Foam Cell Formation by Inducing Autophagy and Modulating PI3K/ATK Signaling

Atherosclerosis (AS) is one of the leading causes of death among the elderly, and is primarily caused by foam cell generation and macrophage inflammation. Rutin is an anti-inflammatory, anti-oxidant, anti-allergic, and antiviral flavonoid molecule, known to have anti-atherosclerotic and autophagy-inducing properties, but its biological mechanism remains poorly understood. In this study, we uncovered that rutin could suppress the generation of inflammatory factors and reactive oxygen species (ROS) in ox-LDL-induced M2 macrophages and enhance their polarization. Moreover, rutin could decrease foam cell production, as shown by oil red O staining. In addition, rutin could increase the number of autophagosomes and the LC3II/I ratio, while lowering p62 expression. Furthermore, rutin could significantly inhibit the PI3K/ATK signaling pathway. In summary, rutin inhibits ox-LDL-mediated macrophage inflammation and foam cell formation by inducing autophagy and modulating PI3K/ATK signaling, showing potential in treating atherosclerosis.     

The Pharmacokinetics in Mice and Cell Uptake of Thymus Immunosuppressive Pentapeptide Using LC-MS/MS Analysis

Thymus immunosuppressive pentapeptide (TIPP) is a novel anti-inflammatory peptide with high efficacy and low toxicity. This study aims to establish a selective LC-MS/MS method for analyzing the analyte TIPP in biological samples, laying the foundation for further PK and PD studies of TIPP. Protein precipitation was conducted in acetonitrile supplemented with 2% formic acid and 25 mg/mL dithiothreitol as a stabilizer, which was followed by backwashing the organic phase using dichloromethane. The chromatographic separation of TIPP was achieved on a C18 column with a gradient elution method. During positive electrospray ionization, TIPP was analyzed via multiple-reaction monitoring. The linear relationships between the concentration of TIPP and peak area in murine plasma cell lysates, supernatants, and the final cell rinse PBS were established within the ranges of 20–5000 ng/mL, 1–200 ng/mL, 10–200 μg/mL, and 0.1–20 ng/mL, respectively (r² > 0.99). Validated according to U.S. FDA guidelines, the proposed method was proved to be acceptable. Such a method had been successfully applied to investigate the pharmacokinetics of TIPP in mice via subcutaneous injection. The plasma half-life in mice was 5.987 ± 1.824 min, suggesting that TIPP is swiftly eliminated in vivo. The amount of TIPP uptake by RBL-2H3 cells was determined using this method, which was also visually verified by confocal. Furthermore, the effective intracellular concentration of TIPP was deduced by comparing the intracellular concentration of TIPP and degrees of inflammation, enlightening further investigation on the intracellular target and mechanism of TIPP.     

Insights into the Allosteric Effect of SENP1 Q597A Mutation on the Hydrolytic Reaction of SUMO1 via an Integrated Computational Study

Small ubiquitin-related modifier (SUMO)-specific protease 1 (SENP1) is a cysteine protease that catalyzes the cleavage of the C-terminus of SUMO1 for the processing of SUMO precursors and deSUMOylation of target proteins. SENP1 is considered to be a promising target for the treatment of hepatocellular carcinoma (HCC) and prostate cancer. SENP1 Gln597 is located at the unstructured loop connecting the helices α4 to α5. The Q597A mutation of SENP1 allosterically disrupts the hydrolytic reaction of SUMO1 through an unknown mechanism. Here, extensive multiple replicates of microsecond molecular dynamics (MD) simulations, coupled with principal component analysis, dynamic cross-correlation analysis, community network analysis, and binding free energy calculations, were performed to elucidate the detailed mechanism. Our MD simulations showed that the Q597A mutation induced marked dynamic conformational changes in SENP1, especially in the unstructured loop connecting the helices α4 to α5 which the mutation site occupies. Moreover, the Q597A mutation caused conformational changes to catalytic Cys603 and His533 at the active site, which might impair the catalytic activity of SENP1 in processing SUMO1. Moreover, binding free energy calculations revealed that the Q597A mutation had a minor effect on the binding affinity of SUMO1 to SENP1. Together, these results may broaden our understanding of the allosteric modulation of the SENP1−SUMO1 complex.     

Application of Two Novel Acoustic Emission Parameters on Identifying the Instability of Granite

The issue of monitoring and early warning of rock instability has received increasing critical attention in the study of rock engineering. To investigate the damage evolution process of granite under triaxial compression tests, acoustic emission (AE) tests were performed simultaneously. This study firstly introduced two novel parameters, i.e., the coefficient of variation (CoV) of the information entropy and correlation dimension of the amplitude data from the AE tests, to identify the precursor of the failure of granite. Then the relationship between the changes in these parameters and the stress-time curve was compared and analyzed. The results of this study show that: (1) There is a strong correlation between the CoV of the information entropy and the failure process of granite. The granite failed when the CoV curve raised to a plateau, which could be used as an indicator of rock instability. (2) The fluctuation of the correlation dimension indicates the different stages during the loading process, i.e., the initial compaction stage, the linear elastic stage, the yield stage, and the failure stage. Each stage contains a descending and a rising process in the correlation dimension curve, and the exhibited starting point or the bottom point at the correlation dimension curve could be selected as the indicator point for the rock instability. (3) The combined analysis of the Information entropy and Correlation dimension can improve the accuracy of rock instability prediction. This study provides new insights into the prediction of rock instability, which has theoretical implications for the stability of subsurface engineering rock masses.     

ACTIVE CONTROL OF A FLEXIBLE CANTILEVER PLATE WITH MULTIPLE TIME DELAYS

Active control of a flexible cantilever plate with multiple time delays is investigated using the discrete optimal control method. A controller with multiple time delays is presented. In this controller, time delay effect is incorporated in the mathematical model of the dynamic system throughout the control design and no approximations and assumptions are made in the controller derivation, so the system stability is easily guaranteed. Furthermore, this controller is available for both small time delays and large time delays. The feasibility and efficiency of the proposed controller are verified through numerical simulations in the end of this paper.     

Dynamic synovial fibroblasts are modulated by NBCn1 as a potential target in rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease characterized by aggressive fibroblast-like synoviocytes (FLSs) and pannus formation. Various therapeutic strategies have been developed against inflammatory cytokines in RA in recent decades. Based on the migratory features of FLSs, we examined whether modulation of the migratory module attenuates RA severity. In this study, inflamed synovial fluid-stimulated FLSs exhibited enhanced migration and migratory apparatus expression, and sodium bicarbonate cotransporter n1 (NBCn1) was identified in primary cultured RA-FLSs for the first time. The NBC inhibitor S0859 attenuated the migration of FLSs induced with synovial fluid from patients with RA or with TNF-α stimulation. Inhibition of NBCs with S0859 in a collagen-induced arthritis (CIA) mouse model reduced joint swelling and destruction without blood, hepatic, or renal toxicity. Primary FLSs isolated from the CIA-induced mouse model also showed reduced migration in the presence of S0859. Our results suggest that inflammatory mediators in synovial fluid, including TNF-α, recruit NBCn1 to the plasma membrane of FLSs to provide dynamic properties and that modulation of NBCn1 could be developed into a therapeutic strategy for RA.Subject terms: Chemotaxis, Bone, Ion channel signalling, Rheumatoid arthritis, Drug development