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The effective transition metal‐free photoredox/bismuth dual catalytic reductive dialkylation of nitroarenes with benzaldehydes has been reported. The nitroarene reduction through visible light‐driven photoredox catalysis was integrated with subsequent reductive dialkylation of anilines under bismuth catalysis to enable the cascade reductive alkylation of nitroarenes with carbonyls. Salient features of this relay catalysis system include mild reaction conditions, no requirement for transition metal catalysts, easy handling, step‐economy, and high selectivity. [ABSTRACT FROM AUTHOR]

Transcriptomic analysis across species is increasingly used to reveal conserved gene regulations which implicate crucial regulators. Cross-species analysis of single-cell RNA sequencing (scRNA-seq) data provides new opportunities to identify the cellular and molecular conservations, especially for cell types and cell type-specific gene regulations. However, few methods have been developed to analyze cross-species scRNA-seq data to uncover both molecular and cellular conservations. Here, we built a tool called CACIMAR, which can perform cross-species analysis of cell identities, markers, regulations, and interactions using scRNA-seq profiles. Based on the weighted sum models of the conserved features, we developed different conservation scores to measure the conservation of cell types, regulatory networks, and intercellular interactions. Using publicly available scRNA-seq data on retinal regeneration in mice, zebrafish, and chick, we demonstrated four main functions of CACIMAR. First, CACIMAR allows to identify conserved cell types even in evolutionarily distant species. Second, the tool facilitates the identification of evolutionarily conserved or species-specific marker genes. Third, CACIMAR enables the identification of conserved intracellular regulations, including cell type-specific regulatory subnetworks and regulators. Lastly, CACIMAR provides a unique feature for identifying conserved intercellular interactions. Overall, CACIMAR facilitates the identification of evolutionarily conserved cell types, marker genes, intracellular regulations, and intercellular interactions, providing insights into the cellular and molecular mechanisms of species evolution. [ABSTRACT FROM AUTHOR]

In recent years, there has been significant focus on China's new drug lag, but relevant research is limited. This study explores the reasons for drug lag by assessing the impact of reforms in China's drug review system, particularly focusing on the influence of clinical development strategies. This study selected drugs first launched in the United States between 2017 and 2022, examining absolute and relative lag between China and the first‐launch country (including submission and review lag). These delays with drugs approved in the European Union and Japan during the same period were compared with uncover the roots of delays in China, further identifying potential factors that could reduce these delays. The results indicate that the National Medical Products Administration (NMPA) has a longer relative lag compared with the European Medicines Agency (EMA) and the Pharmaceuticals and Medical Devices Agency (PMDA). The submission lag time of the NMPA significantly surpasses that of the EMA and PMDA, whereas the review lag time of the NMPA exceeds that of the PMDA but falls short of the EMA. Focusing on clinical trial strategies, bridging trials and multiregional clinical trials (MRCTs) are typically required by the NMPA in East Asia, resulting in longer clinical delay time. Whereas the EMA and PMDA primarily require international MRCTs in Europe and America, with a clinical delay of < 5 months. It is evident that there is a significant gap in clinical trial durations between China and other countries. Further optimization of clinical trial management is necessary to address the lag for new drugs in China. [ABSTRACT FROM AUTHOR]

Biocompatible fatty acids are natural biological materials which exhibit widespread biomedical applications. Nevertheless, their application in vesicle forms is hampered by strong pH sensitivity and poor stability to changes in ionic strength, temperature, and storage. In the investigation, the incorporation of alkyl glycoside (APG), a surfactant with non-ionic properties, into the oleic acid (OA) vesicles was undertaken as a means to address this issue. The newly formed OA/APG composite vesicles form in a pH range of between 5.4 and 7.4, which is close to the pH range of the physiological environment. The stability studies results showed that the OA/APG composite vesicles have excellent stability in terms of ionic strengths, temperature and storage. The formation of NAR-loaded OA/APG composite vesicles was demonstrated through FT-IR, DSC and XRD. In vitro topical delivery and skin retention studies confirmed that the composite vesicles improve skin permeation rate and have better skin permeation behavior. Antioxidant activity experiments confirmed that the antioxidant effect composite vesicles were significantly increased as compared to the naringenin (NAR). This finding has theoretical implications for the use of drug-loaded fatty acid vesicles in cosmetics industries and topical delivery systems. [ABSTRACT FROM AUTHOR]

A rapid and sensitive assessment of the toxicity of oxygenated polycyclic aromatic hydrocarbons (OPAHs), widely distributed persistent organic pollutants in the environment, is crucial for human health. In this study, using high-performance liquid chromatography, the separation and detection of four purines, xanthine (X), guanine (G), adenine (A), and hypoxanthine (HX) in cells were performed. The aim was to evaluate the cytotoxicity of three OPAHs, namely 1,4-benzoquinone (1,4-BQ), 1,2-naphthoquinone (1,2-NQ) and 9,10-phenanthrenequinone (9,10-PQ), with higher environmental concentrations, from the perspective of purine nucleotide metabolism in human skin fibroblast cells (HFF-1). The results revealed that the levels of G and A were low in HFF-1 cells, while the levels of HX and X showed a dose-response relationship with persistent organic pollutants concentration. With increased concentration of the three persistent organic pollutants, the purine metabolism in HFF-1 cells weakened, and the impact of the three persistent organic pollutants on purine metabolism in cells was in the order of 9,10-PQ > 1,4-BQ > 1,2-NQ. This study provided valuable insights into the toxic mechanisms of 1,4-BQ, 1,2-NQ and 9,10-PQ, contributing to the formulation of relevant protective measures and the safeguarding of human health. [ABSTRACT FROM AUTHOR]

The electrochemical detection method of cytotoxicity using intracellular purines as biomarkers has shown great potential for in vitro drug toxicity evaluation. However, no electrochemical detection system based on an in vitro drug metabolism mechanism has been devised. In this paper, electrochemical voltammetry was used to investigate the effect of the S9 system on the electrochemical behavior of HepG2 cells, and benzo[a]pyrene, fluoranthene, and pyrene were employed to investigate the sensitivity of electrochemical signals of cells to the cytotoxicity of drugs metabolized by the S9 system. The results showed that, within 8 h of exposure to the S9 system, the electrochemical signal of HepG2 cells at 0.7 V did not alter noticeably. The levels of xanthine, guanine, hypoxanthine, and adenine in the cells were not significantly altered. Compared with the absence of S9 system metabolism, benzo[a]pyrene and fluoranthene processed by the S9 system decreased the electrochemical signal of the cells in a dose-dependent manner, while pyrene did not change it appreciably. HPLC also revealed that benzo[a]pyrene and fluoranthene metabolized by the S9 system decreased the intracellular purine levels, whereas pyrene had no effect on them before and after S9 system metabolism. The cytotoxicity results of the three drugs examined by electrochemical voltammetry and MTT assay showed a strong correlation and good agreement. The S9 system had no effect on the intracellular purine levels or the electrochemical signal of cells. When the drug was metabolized by the S9 system, variations in cytotoxicity could be precisely detected by electrochemical voltammetry. [ABSTRACT FROM AUTHOR]

Binary ethosome vesicles have been developed as flexible lipid vesicles for the enhanced physicochemical stability and skin delivery of drugs. This work aimed to prepare phloretin-loaded propylene glycol ethosomes (PHL-PGEs) to improve their stability, skin permeability and antioxidant activity. PHL-PGEs were prepared via the ethanol injection method and optimized using different weight ratios of ethanol to propylene glycol (PG). When the ethanol/PG mass ratio changed from 10:0 to 0:10, the encapsulation efficiency and stability of ethosomes increased. At a PHL concentration of 1mg/mL, the EE% was 89.42 ± 2.42 and the DL% was 4.21 ± 0.04, which exhibited their highest values. The encapsulation of the PHL in the PHL-PGEs was strengthened via XRD analysis and FTIR analysis. The results of the in vitro percutaneous permeability test demonstrated that the combined use of ethanol and PG exhibited a notable enhancement in skin permeability, and the skin retention of PHL-PGEs was 1.06 times that of PHL-ethosomes (PHL-Es) and 2.24 times that of the PHL solution. An in vitro antioxidant activity study indicated that solubility and antioxidant activity was potentiated via the nanoencapsulation of phloretin. Therefore, these results confirm the potential of this nanocarrier to enhance physicochemical stability, skin permeability and antioxidant activity. [ABSTRACT FROM AUTHOR]