University of Beihua

The stability of atherosclerotic plaques constitutes the fundamental pathological basis for acute cardiovascular events, and their circadian rhythm characteristics highlight the essential role of dynamic interactions between the host and microorganisms. This review systematically elucidates the multifaceted mechanisms by which disruptions in the circadian rhythm of the gut microbiota contribute to plaque destabilization. Specifically, the microbiota modulates endothelial function, immune homeostasis, and vascular inflammation via rhythmic variations in metabolites. Perturbations in this rhythm compromise the structural integrity of plaques through a synergistic "metabolic-immune-vascular" network. Furthermore, the review unveils the bidirectional regulation between the host's circadian clock and the microbiota's rhythm. Innovatively, we propose "Chronotherapy-based Microbiome Modulation (CMM)," a strategy that reestablishes synchrony between the host and microbiota rhythms through time-restricted feeding, time-specific probiotics, and drugs targeting the circadian clock, thereby, it is possible to improve plaque stability by regulating the host's gut microbiota. The clinical translation of these findings requires overcoming technical challenges, such as personalized time window prediction and microbiota ecological risk assessment, and integrating multi-omics dynamic monitoring with AI modeling and optimization strategies. This review presents a novel perspective on the regulation of plaque stability.

Patients with amyotrophic lateral sclerosis (ALS) often experience difficulty swallowing, making oral administration unsuitable for effective treatment. A transdermal drug delivery system (TDDS) offers a long-acting, non-invasive alternative for ALS therapy. In this study, a riluzole transdermal patch capable of sustained release over 72 h was developed. In vitro skin permeation and pharmacokinetic experiments were conducted to evaluate the impact of various factors-including drug loading, type and concentration of chemical penetration enhancers (CPEs), and type of pressure-sensitive adhesive-on riluzole absorption through the skin. The optimized patch formulation contained 17 % (w/w) riluzole and 10 % (w/w) polyglyceryl-3 dioleate (PGD), with an adhesive layer thickness of 111 μm. The final prescription penetration rate of riluzole was found to be 2.96 μg/(h·cm²). Optimized formulation displayed enhanced stability and prolonged pharmacokinetic performance (C _max = 74.34 ± 13.62 ng/mL, MRT_0-t  = 34.91 ± 11.31 h). No significant skin irritation was observed. The role of PGD in the in vitro release and in vivo transdermal absorption of riluzole was thoroughly investigated. The results revealed that PGD not only reduced the interaction between riluzole and the pressure-sensitive adhesive, enhancing drug release but also increased the fluidity of skin lipids, leading to improved transdermal absorption. This study provides a comprehensive molecular-level understanding of PGD's effect on riluzole permeation, offering valuable insights for the rational selection of CPEs in the development of riluzole TDDS.

Bleomycin (BLM), an essential antitumour medication in clinical applications, has detrimental effects on human health when it appears in an ecological environment, even at trace concentrations. It is desirable to detect trace amounts of BLM by a fast, simple, and efficient method, however, the traditional technologies (e.g., high-performance liquid chromatography, enzyme-linked immunosorbent assay, etc.) generally require expensive equipment and a complicated process, and/or have the disadvantages of long-time running times and poor repeatability. Electrochemical biosensors have been proposed as a fast, easy, sensitive, and cost-effective method for the detection of BLM, and finding a suitable work electrode plays a crucial role in realizing highly performance detection.

In this work, based on a boron-doped diamond (BDD) electrode, coupling with gold (Au) nanoparticles, we design an electrochemical aptasensor for sensitive and specific detection of BLM, featuring a synergistic assembly of aptamers, Au nanoparticles, and BDD film. The BLM aptasensor presents a wide linear range in 1.0 × 10^-17-1.0 × 10^-8 mol L^-1, and achieves a limit of detection as low as 8.5 × 10^-18 mol L^-1. The examinations of trace BLM serum also present a large region of 1.0 × 10^-13-1.0 × 10^-9 mol L^-1. Besides, the interfering tests exibit that the relative responses (RR, %) are ranged from -4.1 % to 6.4 % in five similar structure interfer, and the daily RRs varies between between -3.3 % and 7.3 % in comparison to the 100 % for the first day, which domenstrating the high stability and repeatability and accuracy of the aptasensor.

The innovative aptasensor consisting of β-mercaptohexanol (MCH), Aptamers, Au-NPs, and BDD (MAA-BDD) for the electrochemical detection of trace BLM is of excellent sensitivity, specificity, rigidity, and repeatability, which is suitable for further practical applications on trace BLM detection in various environments.