We have previously demonstrated the anticancer effect of anthocyanins. In this study, we explored the biological activities of delphinidin, the most common of the anthocyanidin monomers, that were related to autophagy in HER-2 positive breast cancer MDA-MB-453 and BT474 cells. The effects of various doses of delphinidin on the proliferation and apoptosis of MDA-MB-453 and BT474 cells were analysed. Autophagy was identified as a critical factor that influenced chemotherapy, and the autophagic mechanism in delphinidin-treated cells was investigated. The autophagy inhibitors, 3-MA and BA1, were used to analyse the effects of autophagy inhibition. Delphinidin inhibited proliferation, promoted apoptosis, and induced autophagy in MDA-MB-453 and BT474 cells in a dose-dependent manner. The inhibition of autophagy enhanced the delphinidin-induced apoptosis and antiproliferative effect in both HER-2 positive breast cancer cells. In addition, delphinidin induced autophagy via suppression of the mTOR signalling pathway and activation of the AMPK signalling pathway in HER-2 positive breast cancer cells. Collectively, the results showed that delphinidin induced apoptosis and autophagy in HER-2 positive breast cancer cells and that autophagy was induced via the mTOR and AMPK signalling pathways. The suppression of autophagy promoted the anticancer effects of delphinidin.

Alzheimer's disease (AD), characterized by β-amyloid (Aβ) aggregation and neuroinflammation, remains a formidable clinical challenge. Herein, we present an innovative nose-to-brain delivery platform utilizing lactoferrin (Lf)-functionalized lipid nanoparticles (LNPs) co-encapsulating α-mangostin (α-M) and β-site APP cleaving enzyme 1 (BACE1) siRNA (siB). This dual-modal therapeutic system synergistically combines the neuroprotective and microglia-reprogramming capabilities of α-M with the transcriptional silencing of BACE1 via siB, thereby simultaneously inhibiting Aβ production and enhancing its clearance. Fabricated via a microfluidic approach, the LNPs exhibited uniform particle size distribution, great encapsulation efficiency, and robust colloidal stability. Upon intranasal administration, Lf-functionalization enabled superior brain-targeting efficacy through receptor-mediated transcytosis. In vitro studies demonstrated that α-M reversed Aβ-induced low-density lipoprotein receptor downregulation, promoting microglial phagocytosis and autophagic degradation of Aβ, while siB effectively suppressed BACE1 expression, abrogating Aβ synthesis. In vivo investigations in APP/PS1 transgenic mice revealed remarkable cognitive recovery, substantial Aβ plaque reduction, and alleviation of neuroinflammation and oxidative stress. This intricately designed LNP system, exploiting a non-invasive and efficient nose-to-brain delivery route, provides a biocompatible, synergistic, and transformative therapeutic strategy for the multifaceted management of AD.

Tumor-associated neutrophils (TANs), pivotal immune cells within the tumor microenvironment (TME), exhibit dual potential in both pro- and anti-tumorigenic effects. These cells display remarkable heterogeneity and plasticity within the TME, adapting to hypoxic and nutrient-deprived conditions through metabolic reprogramming while critically influencing tumor progression, metastasis, and immune evasion. The metabolic reprogramming of TANs not only modulates their functional phenotypes but also reshapes tumor biological behaviors and therapeutic responses by regulating metabolic intermediates and cellular interactions within the TME. Therefore, elucidating the mechanisms underlying TANs metabolic reprogramming has significant implications for deciphering the molecular basis of tumorigenesis, identifying novel therapeutic targets, and optimizing immunotherapeutic strategies. This review systematically summarizes current knowledge regarding metabolic reprogramming mechanisms of TANs in the TME and their impact on tumor progression. We particularly focus on: 1) TAN-specific alterations in glucose, lipid, and amino acid metabolism within the TME; 2) Emerging immunotherapeutic strategies targeting TANs metabolic pathways; 3) Recent advances in understanding TAN-mediated immune evasion and therapy resistance. Furthermore, this review discusses potential challenges and corresponding solutions in targeting TANs metabolic reprogramming for therapeutic intervention, aiming to provide novel insights for advancing cancer immunotherapy.

Fusariummycotoxins, such as trichothecenes, zearalenone (ZEA) and fumonisins, are widely distributed in grain and animal feed and cause hazards to human and animal health. China, one of the largest producers of agricultural products and animal feed, constantly faces challenges in preventing and controllingFusariummycotoxins. The recent status ofFusariummycotoxins in grain and feed is of interest to many stakeholders; however, no comprehensive review of this has been published to date. The objective of this article is to review the recent situation in China, including the contamination situation, its (probable) main causes and the updated regulations. Every district of China has been affected byFusariummycotoxin contamination to varying degrees, with the most seriously affected districts being East China, Central China and North China. The incidence rates of deoxynivalenol and ZEA were higher than those of otherFusariummycotoxins in both grain and feed samples. It has been suggested that deoxynivalenol-3-glucoside should undergo the risk assessment and the development of a related legal limit in China. Among the multiple causes ofFusariummycotoxin occurrence in China, geography and climate and the variable characteristics of plants are probably the two important causes. The latest legal limits forFusariummycotoxins in food were promulgated in 2011, and the legal limits in feed are in the process of being revised. This article aims to provide information for promoting an understanding of the recent situation and the challenges for combatingFusariummycotoxin contamination of grain and feed in China.