Pharmacokinetic Interactions Between Tegoprazan and the Combination of Clarithromycin, Amoxicillin and Bismuth in Healthy Chinese Subjects: An Open-Label, Single-Center, Multiple-Dosage, Self-Controlled, Phase I Trial.

BACKGROUND: Tegoprazan is a potassium-competitive acid blocker that inhibits gastric acid and which may be used for eradicating Helicobacter pylori. This study focuses on the pharmacokinetic interaction and safety between tegoprazan and the combination of clarithromycin, amoxicillin and bismuth in healthy Chinese subjects. METHODS: An open-label, three-period, single-center, multiple-dosage, single-sequence, phase I trial was conducted in 22 healthy subjects. In period 1, the subjects took tegoprazan 50 mg twice daily for 7 days, and in period 2 they were administered clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 600 mg twice daily for 7 days (days 14-20). Tegoprazan, clarithromycin, amoxicillin and bismuth potassium citrate were then administered in combination for 7 days (days 21-27) in period 3. Blood samples were collected up to 12 h after the last dose of each period. Safety assessments were performed in each period. RESULTS: The geometric mean ratios (GMRs) [90% confidence interval (CI)] of maximum plasma concentration at steady state (Cmax,ss) and area under the plasma concentration-time curve over the dosing interval (AUCτ) at steady state were 195.93% (175.52-218.71%) and 287.54% (263.28-314.04%) for tegoprazan and 423.23% (382.57-468.22%) and 385.61% (354.62-419.30%) for tegoprazan metabolite M1, respectively. The GMRs (90% CI) of Cmax,ss and AUCτ were 83.69% (77.44-90.45%) and 110.30% (102.74-118.41%) for clarithromycin, 126.25% (114.73-138.93%) and 146.94% (135.33-159.55%) for 14-hydroxyclarithromycin, 75.89% (69.73-82.60%) and 94.34% (87.94-101.20%) for amoxicillin, and 158.43% (125.43-200.11%) and 183.63% (156.42-215.58%) for bismuth, respectively. All reported adverse events were mild. The frequency of adverse events during the coadministration stage was not higher than that during the single- or triple-drug administration stages. CONCLUSION: The plasma exposure of tegoprazan, M1, 14-hydroxyclarithromycin and bismuth was increased after the coadministration of tegoprazan, clarithromycin, amoxicillin and bismuth. The coadministration exhibited favorable safety and tolerability. CLINICAL TRIALS REGISTRATION: CTR20230643.

Multicomponent Synergistic Antibacterial Hydrogel Based on Gelatin-Oxidized Carboxymethyl Cellulose for Wound Healing of Drug-Resistant Chronic Infection.

Bacterial invasion hinders the healing process of wound, leading to the formation of chronic infected wound; meanwhile, the misuse of antibiotics has resulted in the emergence of numerous drug-resistant bacteria. The application of conventional antimicrobial methods and wound treatment techniques is not appropriate for wound dressings. In this paper, quaternized poly(vinyl alcohol) (QPVA) and pomegranate-like copper uniformly doped polydopamine nanoparticles (PDA@Cu) were introduced into a gelatin-oxidized carboxymethyl cellulose system to form a multicomponent synergistic antibacterial hydrogel (GOQ3P3). Polydopamine improves the biocompatibility and prevents the detachment of Cu nanoparticles. It can achieve synergistic antibacterial effects through quaternary ammonium salt-inorganic nanoparticle photothermal treatment under 808 nm near-infrared (NIR) irradiation. It exhibits highly efficient and rapid bactericidal properties against Escherichia coli, Staphylococcus aureus, and MRSA (methicillin-resistant Staphylococcus aureus) with an antibacterial rate close to 100%. The gel scaffold composed of macromolecules gives the hydrogel excellent mechanical properties, adhesive capabilities, self-healing characteristics, biocompatibility, and pH degradation and promotes cell adhesion and migration. In a full-thickness wound healing model infected with MRSA, GOQ3P3 controls inflammatory responses, accelerates collagen deposition, promotes angiogenesis, and enhances wound closure in the wound healing cascade reaction. This study provides a feasible strategy for constructing dressings targeting chronic infection wounds caused by drug-resistant bacteria.

Guided Wave Characteristic Research and Probabilistic Crack Evaluation in Complex Multi-Layer Stringer Splice Joint Structure.

Multi-layer and multi-rivet connection structures are critical components in the structural integrity of a commercial aircraft, in which elements like skin, splice plate, strengthen patch, and stringer are fastened together layer by layer with multiple rows of rivets for assembling the fuselage and wings. Their non-detachability and inaccessibility pose significant challenges for assessing their health states. Guided wave-based structural health monitoring (SHM) has shown great potential for on-line damage monitoring in hidden structural elements. However, the multi-layer and multi-rivet features introduce complex boundary conditions for guided wave propagation and sensor layouts. Few studies have discussed the guided wave characteristic and damage diagnosis in multi-layer and multi-rivet connection structures. This paper comprehensively researches guided wave propagation characteristics in the multi-layer stringer splice joint (MLSSJ) structure through experiments and numerical simulations for the first time, consequently developing sensor layout rules for such complex structures. Moreover, a Gaussian process (GP)-based probabilistic mining diagnosis method with path-wave band features is proposed. Experiments on a batch of MLSSJ specimens are performed for validation, in which increasing crack lengths are set in each specimen. The results indicate the effectiveness of the proposed probabilistic evaluation method. The maximum root mean squared error of the GP quantitative diagnosis is 1.5 mm.

High salinity gradients and intermediate spatial scales shaped similar biogeographical and co-occurrence patterns of microeukaryotes in a tropical freshwater-saltwater ecosystem.

Microeukaryotes play key ecological roles in the microbial web of aquatic ecosystems. However, large knowledge gaps urgently need to be filled regarding the biogeography with associated shaping mechanisms and co-occurrence patterns of microeukaryotes under freshwater-saltwater gradients, especially true in tropical regions. Here, we investigated microeukaryotes of six mixed freshwater-saltwater regions in the Pearl River Estuary and surrounding coasts in southern China, with salinity ranging 0.1-32.0% and distances spanned up to 500 km, using molecular ecological methods. Results indicate that the biogeography of abundant and rare microeukaryotic communities was similar, both their co-occurrence patterns and biogeographical patterns were driven by deterministic and stochastic processes. The environmental factors with higher selective pressure than dispersal limitation meant that the role of deterministic process in structuring communities was more significant than that of stochastic process, and salinity played important role in structuring both microeukaryotic communities and networks. The abundant communities had stronger influence on entire microeukaryotic communities and seemed to be more sensitive to environmental changes than their rare counterparts, while rare ones had stronger interspecific relationships. Finally, the geographic scale and environmental gradients of study regions should firstly be clarified in future research on the ecological processes of microeukaryotes before conclusions are drawn.

Role of Relational Ties in the Relationship between Thriving at Work and Innovative Work Behavior: An Empirical Study.

Top management in organizations have begun to realize that innovative employees add to the competitive edge of a company which serves to maintain their position in intense market competition. For this purpose, management needs to seek new ways to combine the social environment and employees in the workplace in an inextricable manner that supports innovation. The purpose of this paper was to examine the role of thriving at work and its effects on an individual's innovative behavior. Based on the socially embedded model of thriving, we aimed to assess the relevant related work on structured potential effects with relational ties (i.e., strong versus weak). Particularly, these ties affect the heedful relating differently. This study examined the antecedents of thriving at work and the innovative behavior among employees at a global investment company. Using partial least squares modeling on a sample of 412 observations (strong and weak ties), strong support was found for the theory-driven hypothesized relationships. The results contribute to a better understanding of the relational roles concerning recently emerging constructs of "thriving at work" and "positive organizational scholarship." The implications and limitations of this study are further discussed.

Phylogenetic positions of four hypotrichous ciliates (Protista, Ciliophora) based on SSU rRNA gene, with notes on their morphological characters.

 The morphology and infraciliature of the four hypotrichous ciliates; Rigidohymena inquieta (Stokes, 1887) Berger, 2011, Pattersoniella vitiphila Foissner, 1987, Notohymena australis Foissner & O' Donoghue, 1990, and Cyrtohymena (Cyrtohymenides) australis (Foissner, 1995) Foissner, 2004, collected from east China, were investigated by using live observation and protargol impregnation method. An improved diagnosis for R. inquieta was supplied based on descriptions of present and previous populations. New morphology and morphogenesis information based on Chinese populations of another three hypotrichids were also supplemented. The Small-subunit rRNA (SSU rRNA) gene sequences of the four species were characterized and their phylogenetic positions were revealed by means of Bayesian inference and Maximum-likelihood analysis. The analyses shows that R. inquieta clusters with other members of the subfamily Stylonychinae, which confirms the monophyly of the subfamily and verified R. inquieta as a separated species from R. candens though it differs from others mainly by body size. C. (C.) australis occupying the basal position of the clade which contains cyrtohymenids and some other groups, declines the idea of separating Cyrtohymena into two subgenus. Notohymena australis and China population of Pattersoniella vitiphila respectively clustering with their congeners correspond well with the systematics revealed by morphological similarities.