Customized Intranasal Hydrogel Delivering Methylene Blue Ameliorates Cognitive Dysfunction against Alzheimer's Disease.

The accumulation of hyperphosphorylated tau protein aggregates is a key pathogenic event in Alzheimer's disease (AD) and induces mitochondrial dysfunction and reactive oxygen species overproduction. However, the treatment of AD remains challenging owning to the hindrance caused by the blood-brain barrier (BBB) and the complex pathology of AD. Nasal delivery represents an effective means of circumventing the BBB and delivering drugs to the brain. In this study, black phosphorus (BP) is used as a drug carrier, as well as an antioxidant, and loaded with a tau aggregation inhibitor, methylene blue (MB), to obtain BP-MB. For intranasal (IN) delivery, a thermosensitive hydrogel is fabricated by cross-linking carboxymethyl chitosan and aldehyde Pluronic F127 (F127-CHO) micelles. The BP-MB nanocomposite is incorporated into the hydrogel to obtain BP-MB@Gel. BP-MB@Gel could be injected intranasally, providing high nasal mucosal retention and controlled drug release. After IN administration, BP-MB is continuously released and delivered to the brain, exerting synergistic therapeutic effects by suppressing tau neuropathology, restoring mitochondrial function, and alleviating neuroinflammation, thus inducing cognitive improvements in mouse models of AD. These findings highlight a potential strategy for brain-targeted drug delivery in the management of the complex pathologies of AD.

A critical review of microplastics in the soil-plant system: Distribution, uptake, phytotoxicity and prevention.

Microplastics (MPs) are creating an emerging threat on the soil ecosystems and are of great global concern. However, the distribution in soil-plant system, as well as the phytotoxicity and impact mechanisms of MPs remain largely unexplored so far. This study introduced the diverse sources of MPs and showed the significant spatial variation in the global geographic distribution of MPs contamination based on data collected from 116 studies (1003 sampling sites). We systematically discussed MPs phytotoxicity, such as plant uptake and migration to stems and leaves, delaying seed germination, impeding plant growth, inhibiting photosynthesis, interfering with nutrient metabolism, causing oxidative damage, and producing genotoxicity. We further highlighted the alterations of soil structure and function by MPs, as well as their self and load toxicity, as potential mechanisms that threaten plants. Finally, this paper provided several preventive strategies to mitigate soil MPs pollution and presented research gaps in the biogeochemical behavior of MPs in soil-plant systems. Meanwhile, we recommended that methods for the quantitative detection of MPs accumulated in plant tissues should be explored and established as soon as possible. This review will improve the understanding of the environmental behavior of MPs in soil-plant systems and provide a theoretical reference to better assess the ecological risk of MPs.