纳米药物非临床药代动力学的研究策略及关注要点

随着纳米技术的迅速发展，纳米药物的研发已成为目前药物创新的发展方向之一。纳米药物具有基于纳米结构的尺度效应，其药代动力学特征与普通药物相比存在明显差异，其药代动力学研究与普通药物相比也有其特殊性。本文着重探讨纳米药物的非临床药代动力学的研究策略及关注要点，包括受试物、体内/外试验、生物样本分析、数据评价分析等，期望为研发者提供参考。     

Synergistic effect of high-intensity ultrasound and β-cyclodextrin treatments on browning control in apple juice

This work evaluated the synergistic effects of combined high-intensity ultrasound (HIU) with β-cyclodextrin (β-CD) treatments on inhibiting browning of apple juice and explored the mechanism through simulation system. The combined treatment of 300 W HIU with 0.006 g mL⁻¹ β-CD had a synergistic impact on maintaining juice colour, resulting in a 39.06% reduction in browning degree, only a 36.64% decrease in total phenolic content, and a 17.82% reduction in PPO activity. The inhibition of enzymatic browning in simulated system revealed that HIU suppressed the enzyme (Polyphenol oxidase, PPO) and β-CD inhibited enzyme (PPO) and embedded substrate (polyphenol). The results of spectroscopic analysis showed that the particle-size distribution of PPO narrowed, the content of α-helix in the secondary structure increased, the fluorescence intensity increased, and the maximum wavelength was red-shifted after HIU and β-CD treatment. Changes in structure could further result in PPO activity loss. Hence, the combined treatment could synthetically alleviate the browning of apple juice.     

Electrospun Zn-doped Ga2O3 nanofibers and their application in photodegrading rhodamine B dye

Ultrawide band gap semiconductor materials have attracted considerable attention in recent years owing to their great potential in the photocatalytic field. In this study, Zn-doped Ga₂O₃ nanofibers with various concentrations were synthesized via electrospinning; they exhibited a superior photocatalytic degradation performance of rhodamine B dye compared to that of undoped Ga₂O₃ nanofibers. The Zn dopant replaced Ga sites via replacement doping, which could increase the concentration of oxygen vacancies and lead to enhanced photocatalytic properties. When the Zn concentration increased, a Ga₂O₃/ZnGa₂O₄ hybrid structure formed, which could further enhance the photocatalytic performance. The separation of photogenerated carriers due to Zn doping and heterojunctions were the primary causes of the enhanced photocatalytic performance. This study provides experimental data for the fabrication of high-performance photocatalysts based on Ga₂O₃ nanomaterials.     

药物相互作用研究在新药研发和审评决策中的应用

药物相互作用改变了剂量效应关系，可能会降低疗效或增加毒性，是临床应用中合并用药治疗时重要的考虑因素。预测具有临床意义的药物相互作用是药物研发过程中获益风险评估的重要环节。本文概述了药物研发过程中药物相互作用研究的目的和意义，体内和体外研究的主要内容；梳理分析了2020年国家药品监督管理局（National Medical Products Administration, NMPA）和美国食品药品监督管理局（Food and Drug Administration, FDA）批准上市的新药药物相互作用研究情况，旨在为我国药物研发过程中药物相互作用研究及其监管审评提供参考。     

The Emerging Regulatory Role of Circular RNAs in Periodontal Tissues and Cells

Periodontitis is a chronic complex inflammatory disease associated with a destructive host immune response to microbial dysbiosis, leading to irreversible loss of tooth-supporting tissues. Regeneration of functional periodontal soft (periodontal ligament and gingiva) and hard tissue components (cementum and alveolar bone) to replace lost tissues is the ultimate goal of periodontal treatment, but clinically predictable treatments are lacking. Similarly, the identification of biomarkers that can be used to accurately diagnose periodontitis activity is lacking. A relatively novel category of molecules found in oral tissue, circular RNAs (circRNAs) are single-stranded endogenous, long, non-coding RNA molecules, with covalently circular-closed structures without a 5’ cap and a 3’ tail via non-classic backsplicing. Emerging research indicates that circRNAs are tissue and disease-specific expressed and have crucial regulatory functions in various diseases. CircRNAs can function as microRNA or RNA binding sites or can regulate mRNA. In this review, we explore the biogenesis and function of circRNAs in the context of the emerging role of circRNAs in periodontitis pathogenesis and the differentiation of periodontal cells. CircMAP3K11, circCDK8, circCDR1as, circ_0062491, and circ_0095812 are associated with pathological periodontitis tissues. Furthermore, circRNAs are expressed in periodontal cells in a cell-specific manner. They can function as microRNA sponges and can form circRNA–miRNA–mRNA networks during osteogenic differentiation for periodontal-tissue (or dental pulp)-derived progenitor cells.     

Spatiotemporal Magnetocaloric Microenvironment for Guiding the Fate of Biodegradable Polymer Implants

The degradation behavior of implants is significantly important for bone repair. However, it is still unprocurable to spatiotemporally regulate the degradation of the implants to match bone ingrowth. In this paper, a magneto-controlled biodegradation model is established to explore the degradation behavior of magnetic scaffolds in a magnetothermal microenvironment generated by an alternating magnetic field (AMF). The results demonstrate that the scaffolds can be heated by magnetic nanoparticles (NPs) under AMF, which dramatically accelerated scaffold degradation. Especially, magnetic NPs modified by oleic acid with a better interface compatibility exhibit a greater heating efficiency to further facilitate the degradation. Furthermore, the molecular dynamics simulations reveal that the enhanced motion correlation between magnetic NPs and polymer matrix can accelerate the energy transfer. As a proof-of-concept, the feasibility of magneto-controlled degradation for implants is demonstrated, and an optimizing strategy for better heating efficiency of nanomaterials is provided, which may have great instructive significance for clinical medicine.     

Mesoporous g-C3N4 decorated by Ni2P nanoparticles and CdS nanorods together for enhancing photocatalytic hydrogen evolution

Ni₂P nanoparticles and CdS nanorods were grew together on a mesoporous g-C₃N₄ through a facile in-situ solvothermal approach. Under visible light (λ > 400 nm), the as-prepared ternary PCN–CdS-5% Ni₂P composite displays a high H₂ evolution rate with 2905.86 μmol g^?1 h^?1, which is about 14, 18 and 279 times that of PCN–CdS, PCN–Ni₂P and PCN, respectively. The enhanced photocatalytic activity is mainly attributed to the improved separation efficiency of the photocarriers by the type II PCN–CdS heterojunction and the effective extraction of photogenerated electrons by Ni₂P. Meanwhile, Ni₂P acts as co-catalyst to provide the photocatalytic active site for hydrogen reduction. In addition, PCN–CdS-5% Ni₂P composite exerts good stability in 12-h cycles.