Interrelated Mechanism by Which the Methide Quinone Celastrol,Obtained from the Roots of Tripterygium wilfordii,Inhibits Main Protease 3CLpro of COVID-19 and Acts as Superoxide Radical Scavenger

We describe the potential anti coronavirus disease 2019 (COVID-19) action of the methide quinone inhibitor, celastrol. The related methide quinone dexamethasone is, so far, among COVID-19 medications perhaps the most effective drug for patients with severe symptoms. We observe a parallel redox biology behavior between the antioxidant action of celastrol when scavenging the superoxide radical, and the adduct formation of celastrol with the main COVID-19 protease. The related molecular mechanism is envisioned using molecular mechanics and dynamics calculations. It proposes a covalent bond between the S(Cys145) amino acid thiolate and the celastrol A ring, assisted by proton transfers by His164 and His41 amino acids, and a π interaction from Met49 to the celastrol B ring. Specifically, celastrol possesses two moieties that are able to independently scavenge the superoxide radical: the carboxylic framework located at ring E, and the methide-quinone ring A. The latter captures the superoxide electron, releasing molecular oxygen, and is the feature of interest that correlates with the mechanism of COVID-19 inhibition. This unusual scavenging of the superoxide radical is described using density functional theory (DFT) methods, and is supported experimentally by cyclic voltammetry and X-ray diffraction.     

Effect of Loading Direction,Crown Coverage,and Adjacent Teeth on Stresses in Post-Restored Premolars

Strength of Materials - The aims of this finite elemental stress analysis (FEA) study were to evaluate the effects of loading direction, crown coverage, and adjacent teeth on stress distribution in...     

Genomic merit for reproductive traits. I: Estrous characteristics and fertility in Holstein heifers

Genetic selection of dairy cattle in the United States has included reproductive traits (daughter pregnancy rate, DPR; heifer conception rate, HCR), which is believed to have partly contributed to halting the decline in reproductive performance. The objectives of the current study were to evaluate the association among genomic merit for DPR (GDPR) and HCR (GHCR) with estrous characteristics measured by an automated device. Holstein heifers (n = 1,005) were genotyped at 2 mo of age and were classified into quartiles (Q1 = lowest, Q4 = highest) according to the GDPR and GHCR values of the study population. At 10 to 11 mo of age, heifers were fitted with a collar that recorded activity and rumination and determined the occurrence of estrus according to changes in activity and rumination compared with the individual's baseline values. Estrous characteristics of spontaneous estruses (SPE) and PGF_2α-synchronized estruses (PGSE) were recorded. Heifers had their estrous cycle synchronized with PGF_2α and following detection of estrus received either artificial insemination or embryo transfer according to the herd's genetic selection program. Heifers in Q2 (17.7 ± 0.3 h) of GHCR tended to have longer SPE than heifers in Q4 (16.7 ± 0.3 h). The interaction between GDPR and GHCR was associated with the likelihood of activity peak (0 = no estrus, 100 = maximum activity) ≥80 at SPE because, among heifers in Q3 and Q4 of GHCR, those in Q1 of GDPR were less likely to have an activity peak ≥80. Heifers in Q1 and Q2 of GDPR had reduced hazard of estrus within 7 d of the first PGF_2α treatment compared with heifers in Q4 of GDPR. Heifers in Q1 (16.1 ± 0.4 h) of GDPR had shorter PGSE than heifers in Q2 (17.6 ± 0.4 h) and Q4 (17.4 ± 0.4 h) and tended to have shorter PGSE than heifers in Q3 (17.4 ± 0.4 h). Rumination nadir on the day of PGSE was greater for heifers in Q1 (?30.1 ± 0.9 min/d) of GDPR compared with heifers in Q4 (?33.7 ± 0.9 min/d). Among heifers receiving only artificial insemination, those in Q1 of GHCR (adjusted hazard ratio = 0.65; 95% confidence interval = 0.48–0.88) became pregnant at a slower rate than heifers in Q4. Genomic merit for HCR was negatively associated with SPE but tended to be positively associated with hazard of pregnancy, whereas GDPR was positively associated with PGSE and hazard of estrus. Selection of dairy cattle for DPR and HCR may improve reproductive performance through different pathways, namely estrous characteristics and pregnancy establishment.     

Mapping the development of Open Access in Latin America and Caribbean countries. An analysis of Web of Science Core Collection and SciELO Citation Index (2005–2017)

Scientometrics - Open Access (OA) initiatives and knowledge infrastructure represent vital elements for both producing significant changes in scholarly communication and reducing limitations of...     

Halloysite Nanotubes/Polyethylene Nanocomposites for Active Food Packaging Materials with Ethylene Scavenging and Gas Barrier Properties

Novel polymeric active food packaging films comprising halloysite nanotubes (HNTs) as active agents were developed. HNTs which are hollow tubular clay nanoparticles were utilized as nanofillers absorbing the naturally produced ethylene gas that causes softening and aging of fruits and vegetables; at the same time, limiting the migration of spoilage-inducing gas molecules within the polymer matrix. HNT/polyethylene (HNT/PE) nanocomposite films demonstrated larger ethylene scavenging capacity and lower oxygen and water vapor transmission rates than neat PE films. Nanocomposite films were shown to slow down the ripening process of bananas and retain the firmness of tomatoes due to their ethylene scavenging properties. Furthermore, nanocomposite films also slowed down the weight loss of strawberries and aerobic bacterial growth on chicken surfaces due to their water vapor and oxygen barrier properties. HNT/PE nanocomposite films demonstrated here can greatly contribute to food safety as active food packaging materials that can improve the quality and shelf life of fresh food products.     

Pneumatic motor speed control by trajectory tracking fuzzy logic controller

In this study, trajectory tracking fuzzy logic controller (TTFLC) is proposed for the speed control of a pneumatic motor (PM). A third order trajectory is defined to determine the trajectory function that has to be tracked by the PM speed. Genetic algorithm (GA) is used to find the TTFLC boundary values of membership functions (MF) and weights of control rules. In addition, artificial neural networks (ANN) modelled dynamic behaviour of PM is given. This ANN model is used to find the optimal TTFLC parameters by offline GA approach. The experimental results show that designed TTFLC successfully enables the PM speed track the given trajectory under various working conditions. The proposed approach is superior to PID controller. It also provides simple and easy design procedure for the PM speed control problem.     

Interaction between radiation and drug damage in mammalian cells. II. The effect of actinomycin-D on the repair of the sublethal radiation damage in plateau phase cells

The effect of actinomycin-D (AMD) on radiation damage repair was studied in plateau phase V79 Chinese hamster cells. Sublethal radiation damage repair, as demonstrated by survival fluctuations following two x-ray exposures separted by time, was observed in our plateau phase cells. Plateau phase cells exposed to 0.01-0.04 mug/ml AMD (a nontoxic regimen to 8 hours) between x-ray exposures were less able to repair sublethal damage. If plateau phase cells were plated at low dilutions into fresh medium (conditions for resuming exponential growth) immediately after the first x-ray dose, and exposed to 0.01--0.04 mug/ml AMD until the second dose, inhibition of sublethal damage repair and additional cell killing were observed particularly at 0.04 mug/ml AMD. It is suggested that radiation-drug damage interactions should be studied in plateau phase cells and in cells resuming exponential growth after plateau phase (possibly analogous to "recruitment"), as well as in exponential phase cultures.     

Impact of conditioning regimens and time on adhesion of a fiber post to root dentin using two resin cements

The aim of this study was to evaluate the influence of irrigation protocols on the bond strength of a glass fiber post bonded to dentin using two resin cements. In 200 root-filled teeth, post space was prepared and divided into five groups (n?=?40) based on the irrigation protocol: group 1 (3% sodium hypochlorite), group 2 (3% sodium hypochlorite – 17% Ethylene diamine tetraacetic acid), group 3 (a mixture of sodium hypochlorite and etidronic acid), group 4 (sodium hypochlorite – QMix), and group 5 (distilled water). Samples were subdivided into two subgroups (n?= 10) and fiber posts were cemented using subgroup A (Self-adhesive dual-cure resin cement; SEA) or B (dual-cure resin cement following an etch-and-rinse protocol, ER). Push-out bond strength was performed after 24 h and four months (n?= 10) and failure modes were categorized. Statistical analysis of data was carried out by appropriate analyses (p < 0.05). The irrigation protocol and the resin cement had a significant impact on push-out bond strength. Subgroup A group showed lower bond strength than B at both time periods when 3% NaOCl–17% EDTA and 1:1 mixture of 6% NaOCl + 18%EA protocols were used. Three percent NaOCl used in combination with 17% EDTA or QMix significantly decreased the push-out bond strength of ER at the end of four months (p < 0.05). In conclusion, dual-cure resin cements bonded with etch-and-rinse protocol showed highest bond strength when a mixture of NaOCl and etidronic acid was used as root canal irrigant. These values were differentially influenced by time.