Enhancing Resin Cement Adhesion to Zirconia by Oxygen Plasma-Aided Silicatization.

The combinations of alumina particle air abrasion (AA) and a 10-methacryloyloxyidecyl-dihyidrogenphosphate (MDP) primer and a tribochemical silica coating (TSC) and a silane-base primer are contemporary pre-cementation treatments for zirconia restorations for bonding with resin cements. However, the stability of zirconia resists the mechanical or chemical preparations. The purpose of this study was to develop an atmospheric-pressure oxygen plasma (OP)-aided silicatization method to enhance the adhesion of resin cements to zirconia. Zirconia discs were prepared to receive surface treatments of different combinations: (1) AA or TSC (2) with or without OP treatment, and (3) a chemical primer (no primer, silane, or a silane-MDP mixture). The surface morphology, hydrophilicity, and chemical compositions were characterized, and the resin-zirconia bond strengths were examined either after 24 h or a thermocycling test. The results indicated that the OP treatment after the TSC facilitated the homogeneous distribution of silane and crosslinking of silica particles, and effectively improved the hydrophilicity. The OP increased the O and Si and reduced the C elemental contents, while the combination of TSC, OP, and silane induced SiOx generation. Among the groups, only the TSC-OP-silane treatment effectively enhanced the bond strength and maintained the adhesion after thermocycling. With these results, the OP aided the silicatization protocol effectively, generated silane crosslinking, and resulted in superior resin-zirconia bond strength and durability compared to the current treatments.

Development of Ultrapure and Potent Tannic Acids as a Pan-coronal Antiviral Therapeutic.

The rampageous transmission of SARS-CoV-2 has been devastatingly impacting human life and public health since late 2019. The waves of pandemic events caused by distinct coronaviruses at present and over the past decades have prompted the need to develop broad-spectrum antiviral drugs against them. In this study, our Pentarlandir ultrapure and potent tannic acids (UPPTA) showed activities against two coronaviral strains, SARS-CoV-2 and HCoV-OC43, the earliest-known coronaviruses. The mode of inhibition of Pentarlandir UPPTA is likely to act on 3-chymotrypsin-like protease (3CLpro) to prevent viral replication, as supported by results of biochemical analysis, a 3CLpro assay, and a "gain-of-function" 3CLpro overexpressed cell-based method. Even in the 3CLpro overexpressed environment, Pentarlandir UPPTA remained its antiviral characteristic. Utilizing cell-based virucidal and cytotoxicity assays, the 50% effective concentrations (EC50) and 50% cytotoxicity concentration (CC50) of Pentarlandir UPPTA were determined to be ∼0.5 and 52.5 µM against SARS-CoV-2, while they were 1.3 and 205.9 µM against HCoV-OC43, respectively. In the pharmacokinetic studies, Pentarlandir UPPTA was distributable at a high level to the lung tissue with no accumulation in the body, although the distribution was affected by the food effect. With further investigation in toxicology, Pentarlandir UPPTA demonstrated an overall safe toxicology profile. Taking these findings together, Pentarlandir UPPTA is considered to be a safe and efficacious pancoronal antiviral drug candidate that has been advanced to clinical development.

Effects of silane- and MDP-based primers application orders on zirconia-resin adhesion-A ToF-SIMS study.

OBJECTIVE: To evaluate the 3-methacryloyloxypropyltrimethoxysilane (MPS)- and 10-methacryloyloxydecyl-dihydrogen-phosphate (MDP)-base primers, in their single or sequential applications, with regard to modifying zirconia surfaces and improving resin-zirconia adhesion. METHODS: Zirconia disks received different treatments: without primer (Zr), MPS-base primer (S), MDP-base primer (M), MPS/MDP mixture (SMmix), MPS followed by MDP (SM), and MDP followed by MPS (MS). The compositions and chemical interactions of the coatings to zirconia were analyzed using time-of-flight secondary ion mass spectrometry (ToF-SIMS) and reconstructed 3D ion images. Surface wettability of these coatings to water and resin adhesive was assessed. The shear bond strength (SBS) between resin and the treated zirconia was also examined before and after thermocycling. RESULTS: Groups S and MS presented substantial OH- ions in the coatings and zirconia substrate. PO2- and PO3- fragments existed in all MDP-treatment groups with various proportions and distributions, while groups M and SM showed higher proportions of PO3- and the zirconium phosphate related ions. In 3D ion images, PO3- in groups M and SM was denser and segregated to the interface, but was dispersed or overlaid above PO2- in SMmix and MS. All the primers increased the surface wettability to water and resin, with M and SM presenting superhydrophilic surfaces. All MDP-treatment groups showed improved SBS before thermocycling, while M and SM retained higher SBS after this. SIGNIFICANCE: The MDP-base primer shows a relevant function in facilitating POZr bonding and enhancing resin-zirconia bonding. The co-treated MPS impairs the chemical activity of MDP, especially if it is the final coat.

Predicting the redox state and secondary structure of cysteine residues using multi-dimensional classification analysis of NMR chemical shifts.

A tool for predicting the redox state and secondary structure of cysteine residues using multi-dimensional analyses of different combinations of nuclear magnetic resonance (NMR) chemical shifts has been developed. A data set of cysteine [Formula: see text], (13)C(α), (13)C(ß), (1)H(α), (1)H(N), and (15)N(H) chemical shifts was created, classified according to redox state and secondary structure, using a library of 540 re-referenced BioMagResBank (BMRB) entries. Multi-dimensional analyses of three, four, five, and six chemical shifts were used to derive rules for predicting the structural states of cysteine residues. The results from 60 BMRB entries containing 122 cysteines showed that four-dimensional analysis of the C(α), C(ß), H(α), and N(H) chemical shifts had the highest prediction accuracy of 100 and 95.9 % for the redox state and secondary structure, respectively. The prediction of secondary structure using 3D, 5D, and 6D analyses had the accuracy of ~90 %, suggesting that H(N) and [Formula: see text] chemical shifts may be noisy and made the discrimination worse. A web server (6DCSi) was established to enable users to submit NMR chemical shifts, either in BMRB or key-in formats, for prediction. 6DCSi displays predictions using sets of 3, 4, 5, and 6 chemical shifts, which shows their consistency and allows users to draw their own conclusions. This web-based tool can be used to rapidly obtain structural information regarding cysteine residues directly from experimental NMR data.

Type I and II ß-turns prediction using NMR chemical shifts.

A method for predicting type I and II ß-turns using nuclear magnetic resonance (NMR) chemical shifts is proposed. Isolated ß-turn chemical-shift data were collected from 1,798 protein chains. One-dimensional statistical analyses on chemical-shift data of three classes ß-turn (type I, II, and VIII) showed different distributions at four positions, (i) to (i + 3). Considering the central two residues of type I ß-turns, the mean values of Cο, Cα, H(N), and N(H) chemical shifts were generally (i + 1) > (i + 2). The mean values of Cß and Hα chemical shifts were (i + 1) < (i + 2). The distributions of the central two residues in type II and VIII ß-turns were also distinguishable by trends of chemical shift values. Two-dimensional cluster analyses on chemical-shift data show positional distributions more clearly. Based on these propensities of chemical shift classified as a function of position, rules were derived using scoring matrices for four consecutive residues to predict type I and II ß-turns. The proposed method achieves an overall prediction accuracy of 83.2 and 84.2% with the Matthews correlation coefficient values of 0.317 and 0.632 for type I and II ß-turns, indicating that its higher accuracy for type II turn prediction. The results show that it is feasible to use NMR chemical shifts to predict the ß-turn types in proteins. The proposed method can be incorporated into other chemical-shift based protein secondary structure prediction methods.

Robust stabilization for a class of nonlinear systems via a single input control applicable to chaotic systems and its circuit implementation.

In this study, the concept of global exponential ε-stabilization is introduced and the robust stabilization for a class of nonlinear systems with single input is investigated. Based on Lyapunov-like Theorem with differential and integral inequalities, a feedback control is proposed to realize the global stabilization of such nonlinear systems with any pre-specified exponential convergence rate. The guaranteed exponential convergence rate can be also correctly estimated. This result can be straightforwardly applicable to some famous chaotic systems. Besides, it will be proven that a single and linear control, with lower dimensions than that of the states, can realize the global exponential stability of some famous chaotic systems. Finally, comparisons of our main results with recently published results as well as numerical examples with circuit realization are provided to show the effectiveness and superiority of the obtained results.

A secure and efficient password-based user authentication scheme using smart cards for the integrated EPR information system.

The integrated EPR information system supports convenient and rapid e-medicine services. A secure and efficient authentication scheme for the integrated EPR information system provides safeguarding patients' electronic patient records (EPRs) and helps health care workers and medical personnel to rapidly making correct clinical decisions. Recently, Wu et al. proposed an efficient password-based user authentication scheme using smart cards for the integrated EPR information system, and claimed that the proposed scheme could resist various malicious attacks. However, their scheme is still vulnerable to lost smart card and stolen verifier attacks. This investigation discusses these weaknesses and proposes a secure and efficient authentication scheme for the integrated EPR information system as alternative. Compared with related approaches, the proposed scheme not only retains a lower computational cost and does not require verifier tables for storing users' secrets, but also solves the security problems in previous schemes and withstands possible attacks.

Simple group password-based authenticated key agreements for the integrated EPR information system.

The security and privacy are important issues for electronic patient records (EPRs). The goal of EPRs is sharing the patients' medical histories such as the diagnosis records, reports and diagnosis image files among hospitals by the Internet. So the security issue for the integrated EPR information system is essential. That is, to ensure the information during transmission through by the Internet is secure and private. The group password-based authenticated key agreement (GPAKE) allows a group of users like doctors, nurses and patients to establish a common session key by using password authentication. Then the group of users can securely communicate by using this session key. Many approaches about GAPKE employ the public key infrastructure (PKI) in order to have higher security. However, it not only increases users' overheads and requires keeping an extra equipment for storing long-term secret keys, but also requires maintaining the public key system. This investigation presents a simple group password-based authenticated key agreement (SGPAKE) protocol for the integrated EPR information system. The proposed SGPAKE protocol does not require using the server or users' public keys. Each user only remembers his weak password shared with a trusted server, and then can obtain a common session key. Then all users can securely communicate by using this session key. The proposed SGPAKE protocol not only provides users with convince, but also has higher security.

Room-temperature super-extraction system (RTSES) optimizes the anxiolytic- and antidepressant-like behavioural effects of traditional Xiao-Yao-San in mice.

BACKGROUND: Xiao-Yao-San (XYS) is a Chinese medicinal formula for treating anxiety and depression. This study aims to evaluate the use of a room-temperature super-extraction system (RTSES) to extract the major active components of XYS and enhance their psycho-pharmacological effects. METHODS: The neuroprotective roles of XYS/RTSES against reserpine-derived neurotoxicity were evaluated using a glial cell injury system (in vitro) and a depression-like C57BL/6 J mouse model (in vivo). The anxiolytic-behavioural effects were measured by the elevated plus-maze (EPM) test and the antidepressant effects were evaluated by the forced swimming test (FST) and tail suspension test (TST). Glucose tolerance and insulin resistance were assayed by ELISA. The expression of 5-HT1A receptors in the prefrontal cortex was examined by western blotting. RESULTS: XYS/RTSES (300 µg/mL) diminished reserpine-induced glial cell death more effectively than either XYS (300 µg/mL) or fluoxetine (30 µM) at 24 h (P = 0.0481 and P = 0.054, respectively). Oral administration of XYS/RTSES (500 mg/kg/day) for 4 consecutive weeks significantly elevated the ratios of entries (open arms/closed arms; P = 0.0177) and shuttle activity (P = 0.00149) on the EPM test, and reduced the immobility time by 90% on the TST (P = 0.00000538) and FST (P = 0.0000053839). XYS/RTSES also improved the regulation of blood glucose (P = 0.0305) and increased the insulin sensitivity (P = 0.0093). The Western blot results indicated that the activation of cerebral 5-HT1A receptors may be involved in the mechanisms of XYS/RTSES actions. CONCLUSION: The RTSES could provide a novel method for extracting effective anxiolytic- and antidepressant-like substances. XYS/RTSES improved the regulation of blood glucose and increased the insulin sensitivity in reserpine-induced anxiety and depression. Neuroprotection of glial cells and activation of cerebral 5-HT1A receptors were also involved.

Effects of amisulpride on the cognitive function of patients with schizophrenia who switched from risperidone.

Objectives. The aims of this 13-week study were to examine the efficacy and safety of amisulpride, and effects on cognitive function in patients with schizophrenia after they switched from risperidone. Methods. Twenty-three patients with schizophrenia whose antipsychotic was switched from risperidone to amisulpride were recruited. The efficacy, safety, and cognitive function were assessed. Results. Significant improvements were noted in the PANSS, CGI-S, and MADRS. The prolactin level, but not any of the remaining laboratory variables, increased significantly. The cognitive function improved significantly, particularly in memory subtests. Conclusions. Switching antipsychotic from risperidone to amisulpride in schizophrenia might have significantly improved not only the efficacy, but also various domains of cognitive function. However, hyperprolactinemia existed and was sometimes even worse.

2DCSi: identification of protein secondary structure and redox state using 2D cluster analysis of NMR chemical shifts.

Chemical shifts of amino acids in proteins are the most sensitive and easily obtainable NMR parameters that reflect the primary, secondary, and tertiary structures of the protein. In recent years, chemical shifts have been used to identify secondary structure in peptides and proteins, and it has been confirmed that (1)H(alpha), (13)C(alpha), (13)C(beta), and (13)C' NMR chemical shifts for all 20 amino acids are sensitive to their secondary structure. Currently, most of the methods are purely based on one-dimensional statistical analyses of various chemical shifts for each residue to identify protein secondary structure. However, it is possible to achieve an increased accuracy from the two-dimensional analyses of these chemical shifts. The 2DCSi approach performs two-dimension cluster analyses of (1)H(alpha), (1)H(N), (13)C(alpha), (13)C(beta), (13)C', and (15)N(H) chemical shifts to identify protein secondary structure and the redox state of cysteine residue. For the analysis of paired chemical shifts of 6 data sets, each of the 20 amino acids has its own 15 two-dimension cluster scattering diagrams. Accordingly, the probabilities for identifying helix and extended structure were calculated by using our scoring matrix. Compared with existing the chemical shift-based methods, it appears to improve the prediction accuracy of secondary structure identification, particularly in the extended structure. In addition, the probability of the given residue to be helix or extended structure is displayed, allows the users to make decisions by themselves.

Predicting the redox state and secondary structure of cysteine residues in proteins using NMR chemical shifts.

We report 2D cluster analyses of 1Halpha, 1HN, 13Calpha, and 13C' versus 13Cbeta NMR chemical shifts (CSs) that can be used to predict the redox state and secondary structure of cysteine residues in proteins. A database of cysteine 1Halpha, 1Hbeta2, 1Hbeta3, 1HN, 13Calpha, 13Cbeta, 13C', and 15NH CSs as a function of secondary structure and redox state was constructed from BioMagResBank entries. One-dimensional statistical analysis showed that cysteine 1Halpha, 1HN, 13Calpha, 13C', and 15NH CSs reflected the secondary structure, and that cysteine Cbeta CS is extremely sensitive to the redox state. In contrast, cysteine 1Hbeta CS was not correlated with its redox state or secondary structure. Two-dimensional cluster analysis revealed that 2D Calpha/Cbeta, C'/Cbeta, HNu/Cbeta, and Halpha/Cbeta clusters were helpful in distinguishing both the redox state and secondary structure of cysteine residues. Based on these results, we derived rules using a score matrix to predict the redox state and secondary structure of cysteines using their CSs. The score matrix predicts the redox state and secondary structure of cysteine residues in proteins with approximately 90% accuracy. This suggests that the redox state and secondary structure of cysteine residues in peptides and proteins can be obtained from their CSs without recourse to nuclear Overhauser effect measurements.

Discovery of potent, nonsystemic apical sodium-codependent bile acid transporter inhibitors (Part 1).

Elevated plasma levels of low-density lipoprotein (LDL) cholesterol are a major risk factor for atherosclerosis leading to coronary artery disease (CAD), which remains the main cause of mortality in Western society. We believe that by preventing the reabsorption of bile acids, a minimally absorbed apical sodium-codependent bile acid transporter (ASBT) inhibitor would lower the serum cholesterol without the potential systemic side effects of an absorbed drug. A series of novel benzothiepines (3R,3R'-2,3,4,5-tetrahydro-5-aryl-1-benzothiepin-4-ol 1,1-dioxides) were synthesized and tested for their ability to inhibit the apical sodium dependent bile acid transport (ASBT)-mediated uptake of [(14)C]taurocholate (TC) in H14 cells. A 3R,4R,5R/3S,4S,5S racemate was found to have greater potency than the other three possible racemates. Addition of electron-donating groups such as a dimethylamino substituent at the 7 position greatly enhanced potency, and incorporation of a long-chain quaternary ammonium substituent on the 5-phenyl ring was useful in minimizing systemic exposure of this locally active ASBT inhibitor while also increasing water solubility and maintaining potency. The reported results describe the synthesis and SAR development of this benzothiepine class of ASBT inhibitors resulting in an 6000-fold improvement in ASBT inhibition with desired minimal systemic exposure of this locally acting drug candidate.

Discovery of potent, nonsystemic apical sodium-codependent bile acid transporter inhibitors (Part 2).

In the preceding paper several compounds were reported as potent apical sodium-codependent bile acid transporter (ASBT) inhibitors. Since the primary site for active bile acid reabsorption is via ASBT, which is localized on the luminal surface of the distal ileum, we reasoned that a nonsystemic inhibitor would be desirable to minimize or eliminate potential systemic side effects of an absorbed drug. To ensure bioequivalency and product stability, it was also essential that we identify a nonhygroscopic inhibitor in its most stable crystalline form. A series of benzothiepines were prepared to refine the structure-activity relationship of the substituted phenyl ring at the 5-position of benzothiepine ring and to identify potent, crystalline, nonhygroscopic, and efficacious ASBT inhibitors with low systemic exposure.