Blocking Metallothionein-2 Expression by Copper-Doped Carbon Dots Induces Cellular Antioxidant System Collapse for Antitumor Therapy.

The insufficient antioxidant reserves in tumor cells play a critical role in reactive oxygen species (ROS)-mediated therapeutics. Metallothionein-2 (MT-2), an intracellular cysteine-rich protein renowned for its potent antioxidant properties, is intricately involved in tumor development and correlates with a poor prognosis. Consequently, MT-2 emerges as a promising target for tumor therapy. Herein, we present the development of copper-doped carbon dots (Cu-CDs) to target MT-2 to compromise the delicate antioxidant reserves in tumor cells. These Cu-CDs with high tumor accumulation and prolonged body retention can effectively suppress tumor growth by inducing oxidative stress. Transcriptome sequencing unveils a significant decrease in MT-2 expression within the in vivo tumor samples. Further mechanical investigations demonstrate that the antitumor effect of Cu-CDs is intricately linked to apolipoprotein E (ApoE)-mediated downregulation of MT-2 expression and the collapse of the antioxidant system. The robust antitumor efficacy of Cu-CDs provides invaluable insights into developing MT-2-targeted nanomedicine for cancer therapies.

AI-Powered Microfluidics: Shaping the Future of Phenotypic Drug Discovery.

Phenotypic drug discovery (PDD), which involves harnessing biological systems directly to uncover effective drugs, has undergone a resurgence in recent years. The rapid advancement of artificial intelligence (AI) over the past few years presents numerous opportunities for augmenting phenotypic drug screening on microfluidic platforms, leveraging its predictive capabilities, data analysis, efficient data processing, etc. Microfluidics coupled with AI is poised to revolutionize the landscape of phenotypic drug discovery. By integrating advanced microfluidic platforms with AI algorithms, researchers can rapidly screen large libraries of compounds, identify novel drug candidates, and elucidate complex biological pathways with unprecedented speed and efficiency. This review provides an overview of recent advances and challenges in AI-based microfluidics and their applications in drug discovery. We discuss the synergistic combination of microfluidic systems for high-throughput screening and AI-driven analysis for phenotype characterization, drug-target interactions, and predictive modeling. In addition, we highlight the potential of AI-powered microfluidics to achieve an automated drug screening system. Overall, AI-powered microfluidics represents a promising approach to shaping the future of phenotypic drug discovery by enabling rapid, cost-effective, and accurate identification of therapeutically relevant compounds.

Revisited and innovative perspectives of oral ulcer: from biological specificity to local treatment.

Mouth ulcers, a highly prevalent ailment affecting the oral mucosa, leading to pain and discomfort, significantly impacting the patient's daily life. The development of innovative approaches for oral ulcer treatment is of great importance. Moreover, a deeper and more comprehensive understanding of mouth ulcers will facilitate the development of innovative therapeutic strategies. The oral environment possesses distinct traits as it serves as the gateway to the digestive and respiratory systems. The permeability of various epithelial layers can influence drug absorption. Moreover, oral mucosal injuries exhibit distinct healing patterns compared to cutaneous lesions, influenced by various inherent and extrinsic factors. Furthermore, the moist and dynamic oral environment, influenced by saliva and daily physiological functions like chewing and speaking, presents additional challenges in local therapy. Also, suitable mucosal adhesion materials are crucial to alleviate pain and promote healing process. To this end, the review comprehensively examines the anatomical and structural aspects of the oral cavity, elucidates the healing mechanisms of oral ulcers, explores the factors contributing to scar-free healing in the oral mucosa, and investigates the application of mucosal adhesive materials as drug delivery systems. This endeavor seeks to offer novel insights and perspectives for the treatment of oral ulcers.