Regulation of Polysaccharide in Wu-Tou Decoction on Intestinal Microflora and Pharmacokinetics of Small Molecular Compounds in AIA Rats

Wu-tou decoction (WTD), a traditional Chinese medicine prescription, is used to treat rheumatoid arthritis (RA). It works by controlling intestinal flora and its metabolites, which in turn modulates the inflammatory response and intestinal barrier function. Small molecular compounds (SM) and polysaccharides (PS) were the primary constituents of WTD extract. In this work, a model of adjuvant-induced arthritis (AIA) in rats was established and treated with WTD, SM, and PS, respectively. 16S rRNA gene sequencing was used to examine the regulatory impact of the various groups on the disturbance of the gut flora induced by RA. Further, since PS cannot be absorbed into the blood, the influence of PS on the absorption and metabolism of SM was studied by examining their pharmacokinetic (PK) parameters of 23 active components in SM by UPLC-MS/MS. WTD was found to be more effective than PS and SM in alleviating arthritis in AIA rats, which may be related to changes in gut flora. The PK properties of 13 active compounds were altered after PS intervene. Based on the findings, PS may be able to manage the disruption of intestinal microbiota, enhance the intestinal environment of model animals, and hence influence SM absorption and metabolism

TIR/BB-Loop Mimetic AS-1 Attenuates Cardiac Ischemia/Reperfusion Injury via a Caveolae and Caveolin-3-Dependent Mechanism

AS-1, the TIR/BB loop mimetic, plays a protective role in cardiac ischemia/reperfusion (I/R) but the molecular mechanism remains unclear. The muscle specific caveolin3 (Cav-3) and the caveolae have been found to be critical for cardioprotection. This study aimed to evaluate our hypothesis that caveolae and Cav-3 are essential for AS-1-induced cardioprotection against myocardial I/R injury. To address these issues, we analyzed the involvement of Cav-3 in AS-1 mediated cardioprotection both in vivo and in vitro. We demonstrate that AS-1 administration significantly decreased infarct size, improved cardiac function after myocardial I/R and modulated membrane caveolae and Cav-3 expression in the myocardium. For in vitro studies, AS-1 treatment prevented Cav-3 re-distribution induced by H/R injury. In contrast, disruption of caveolae by MCD treatment or Cav-3 knockdown abolished the protection against H/R-induced myocytes injury by AS-1. Our findings reveal that AS-1 attenuates myocardial I/R injury through caveolae and Cav-3 dependent mechanism

Oregano essential oil modulates colonic homeostasis and intestinal barrier function in fattening bulls

Oregano essential oil (OEO) primarily contains phenolic compounds and can serve as a dietary supplement for fattening bulls. However, the precise molecular mechanism underlying this phenomenon remains largely elusive. Therefore, this study investigated the impact of adding OEO to diet on the integrity of the intestinal barrier, composition of the colonic microbiome, and production of microbial metabolites in fattening bulls. Our goal was to provide insights into the utilization of plant essential oil products in promoting gastrointestinal health and welfare in animals. We employed amplicon sequencing and metabolome sequencing techniques to investigate how dietary supplementation with OEO impacted the intestinal barrier function in bulls. The inclusion of OEO in the diet resulted in several notable effects on the colon of fattening bulls. These effects included an increase in the muscle thickness of the colon, goblet cell number, short-chain fatty acid concentrations, digestive enzyme activity, relative mRNA expression of intestinal barrier-related genes, and relative expression of the anti-inflammatory factor IL-10. Additionally, α-amylase activity and the relative mRNA expression of proinflammatory cytokines decreased. Moreover, dietary OEO supplementation increased the abundance of intestinal Bacteroides, Coprobacillus, Lachnospiraceae_UCG_001, and Faecalitalea. Metabolomic analysis indicated that OEO primarily increased the levels of 5-aminovaleric acid, 3-methoxysalicylic acid, and creatinine. In contrast, the levels of maltose, lactulose, lactose, and D-trehalose decreased. Correlation analysis showed that altered colonic microbes and metabolites affected intestinal barrier function. Taken together, these results demonstrate that OEO facilitates internal intestinal environmental homeostasis by promoting the growth of beneficial bacteria while inhibiting harmful ones

Tuning of influenza A virus neuraminidase activity

Influenza A viruses (IAVs) are zoonotic pathogens that constantly circulate in a wide variety of species, including birds, pigs and humans. In humans, IAVs cause seasonal epidemics and occasional influenza pandemics. Annual epidemics caused by seasonal IAVs usually lead to millions of human infections, posing great threats to public health and cause large economic burdens. Influenza pandemic occurs when animal viruses managed to cross the host species barrier and became transmissible among humans. IAV pandemics have occurred four times in the 100 years, causing millions of deaths and global devastating effects. IAVs are enveloped, segmented negative-strand RNA viruses belonging to the Orthomyxoviridae family. There are two main important glycoproteins in the IAV virus membrane, hemagglutinin (HA) and neuraminidase (NA), both of which recognize sialic acids (SIAs). The HA protein is responsible for virus-cell attachment via binding to sialylated receptors at the cell surface. The NA protein is the receptor-destroying enzyme and responsible for removing SIA from host glycoproteins as well as glycolipids, thereby allowing release of progeny virions from cells and decoy receptors and preventing virus self-aggregation. A functional balance between the HA and NA proteins is of importance for maintaining optimal virus replication as well as transmission across different host speciesADDIN RW.CITE{{36 Xu,R. 2012; 37 Yen,H.L. 2011; 38 de Wit,E. 2010}}. While HA receptor-binding avidity and specificity have been studied in detail, much less is known about the molecular determinants that mediate (changes in) the specificity and activity of IAV NA proteins. The overall aim of this thesis was to unravel to what extent and how IAVs modulate the activity of their NA proteins during virus evolution. To this end, NA functionality, mainly enzymatic activity has been extensively investigated by using an optimized recombinant soluble protein approach. By doing so, we not only identified an optimal recombinant soluble NA expression approach, but also identified residues that affected NA folding and/or enzymatic activity. With the established recombinant soluble approach, we further found an important role of the 2nd SIA-binding site in NA enzymatic activity. Mutation of the 2nd SIA binding site provides viruses with an additional mechanism to manipulate the enzymatic activity of their NA proteins without having to mutate their active site residues directly. The studies presented in this thesis also highlight some complexities of HA/NA balance during virus evolution. Different NA phenotypic properties of H1N1pdm09 virus were found to be intertwined, with several NA substitutions affecting more than one phenotypic characteristic. The phenotypic changes of NA are probably also linked to the properties of the HA protein and corresponding HA/NA balance, which makes evolution of HA and NA more difficult to understand

RESEARCHES ON COMPRESSIVE MECHANICAL BEHAVIORS OF ADHESIVE BONDED THIN-WALLED HOLLOW SPHERES STRUCTURE

Compressive mechanical properties of thin-walled hollow spheres structure were researched by experiment and finite element method. Ping-Pong balls were selected and bonded together with a linking neck to comprise the ideal model of thinwalled hollow spheres structure. The experimental result validated the effectiveness of the finite element model. The effects of the material and geometry parameters of the hollow spheres and the linking neck were then investigated by finite element method. The results reveal that:（ 1） the deformation process of the structure includes four stages: elastic deformation,axisymmetric buckling,forming non-axisymmetric polygon and transforming to axisymmetric mode;（ 2） the elastic modulus and yield stress basically increase with the hollow sphere wall thickness,linking neck radius and center thickness as well as the Young’s modulus and yield stress of spheres material;（ 3） the strain of structural self-contact behavior increases with the linking neck center thickness and radius

Efficient Evaluation of Concrete Fracture Surface Roughness Using Fringe Projection Technology

The evaluation of concrete surface roughness is crucial in the field of civil engineering. The purpose of this study is to propose a no-contact and efficient method for the measurement of the roughness of concrete fracture surfaces based on fringe-projection technology. A simple phase-correction method using one additional strip image is presented for the phase unwrapping to improve the measurement efficiency and accuracy. The experimental results indicate that the measuring error for plane height is less than 0.1mm, and the relative accuracy for measuring a cylindrical object is about 0.1%, meeting the requirements for concrete fracture-surface measurement. On this basis, three-dimensional reconstructions were carried out on various concrete fracture surfaces to evaluate the roughness. The results reveal that the surface roughness (R) and fractal dimension (D) decrease as the concrete strength increases or the water-to-cement ratio decreases, consistent with previous studies. In addition, compared with the surface roughness, the fractal dimension is more sensitive to the change in concrete surface shape. The proposed method is effective for detecting concrete fracture-surface features