CoFeSe2 @DMSA@FA Nanocatalyst for Amplification of Oxidative Stress to Achieve Multimodal Tumor Therapy.

Nanomedicine has significantly advanced precise tumor therapy, providing essential technical blessing for active drug accumulation, targeted consignment, and mitigation of noxious side effects. To enhance anti-tumor efficacy, the integration of multiple therapeutic modalities has garnered significant attention. Here, we designed an innovative CoFeSe2 @DMSA@FA nanocatalyst with Se vacancies (abbreviated as CFSDF), which exhibits synergistic chemodynamic therapy (CDT) and photothermal therapy (PTT), leading to amplified tumor oxidative stress and enhanced photothermal effects. The multifunctional CFSDF nanocatalyst exhibits the remarkable ability to catalyze the Fenton reaction within the acidic tumor microenvironment, efficiently converting hydrogen peroxide (H2 O2 ) into highly harmful hydroxyl radicals (⋅OH). Moreover, the nanocatalyst effectively diminishes GSH levels and ameliorates intracellular oxidative stress. The incorporation of FA modification enables CFSDF to evade immune detection and selectively target tumor tissues. Numerous in vitro and in vivo investigations have consistently demonstrated that CFSDF optimizes its individual advantages and significantly enhances therapeutic efficiency through synergistic effects of multiple therapeutic modalities, offering a valuable and effective approach to cancer treatment.

Precisely designed Fex (x = 1-2) cluster nanocatalysts for effective nanocatalytic tumor therapy.

Atomically dispersed metal clusters are considered as promising nanocatalysts due to their excellent physicochemical properties. Here, we report a novel strategy for precisely designing Fex (x = 1-2) cluster nanocatalysts (Fe1-N-C and Fe2-N-C) with dual catalytic activity, which can catalyze H2O2 into reactive oxygen species (ROS) and oxidize glutathione (GSH) into glutathione disulfide simultaneously. The adsorption energies of Fe-N sites in Fe2-N-C for GSH and H2O2 intermediates were well controlled due to the orbital modulation of adjacent Fe sites, contributing to the higher dual catalytic activity compared to Fe1-N-C. Additionally, tamoxifen (TAM) was loaded into Fe2-N-C (Fe2@TDF NEs) to down-regulate the intracellular pH for higher Fenton-like catalytic efficiency and ROS production. The generated ROS could induce apoptosis and lipid peroxidation, triggering ferroptosis. Meanwhile, upregulation of ROS and lipid peroxidation, along with GSH depletion and GPX4 downregulation could promote the apoptosis and ferroptosis of tumor cells. In addition, the lactic acid accumulation effect of TAM and the high photothermal conversion ability of Fe2@TDF NEs could further enhance the catalytic activity to achieve synergistic antitumor effects. As a result, this work highlights the critical role of adjacent metal sites at the atomic-level and provides a rational guidance for the design and application of nanocatalytic antitumor systems.

Precision therapy through breaking the intracellular redox balance with an MOF-based hydrogel intelligent nanobot for enhancing ferroptosis and activating immunotherapy.

With the advancement and development of nanomedicine, tumor precision therapy provides technical support for effective accumulation and targeted drug delivery, and reduces toxic side effects. In cancer cells, breaking the redox balance could induce cancer cell death. Herein, a novel iron-containing intelligent hydrogel nanobot (FeSe2-Ce6/MOF@HA/PEI/CpG@HHPA NPs, abbreviated as FSMH) is proposed to break the intracellular redox balance and trigger the immune response. The as-fabricated multifunctional FSMH could not only exert Fenton reactions in the acidic tumor microenvironment, converting hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (˙OH), but also effectively consume GSH to attenuate the intracellular oxidative stress. The negative charge of the FSMH nanohydrogel system guarantees its superexcellent stabilization in blood circulation and optimal tumor collection. Subsequently, the surface charge of the endocytosed FSMH was transformed to a positive charge after exposure to the acidic tumor environment, further improving its tumor collection and locally releasing Fe ions and immune adjuvants. Furthermore, Ce6 was released in a pH-responsive manner in the acidic microenvironment. In the presence of near-infrared light, singlet oxygen was produced by the FSMH nanohydrogel system, to ablate tumors and promote the maturation of dendritic cells, achieving the precision-combined strategies effect of CDT, PDT, and immunotherapy.

A Comprehensive Review of Lipidomics and Its Application to Assess Food Obtained from Farm Animals.

Lipids are one of the major macronutrients essential for adequate growth and maintenance of human health. Their structure is not only complex but also diverse, which makes systematic and holistic analyses challenging; consequently, little is known regarding the relationship between phenotype and mechanism of action. In recent years, rapid advancements have been made in the fields of lipidomics and bioinformatics. In comparison with traditional approaches, mass spectrometry-based lipidomics can rapidly identify as well as quantify >1,000 lipid species at the same time, facilitating comprehensive, robust analyses of lipids in tissues, cells, and body fluids. Accordingly, lipidomics is now being widely applied in various fields, particularly food and nutrition science. In this review, we discuss lipid classification, extraction techniques, and detection and analysis using lipidomics. We also cover how lipidomics is being used to assess food obtained from livestock and poultry. The information included herein should serve as a reference to determine how to characterize lipids in animal food samples, enhancing our understanding of the application of lipidomics in the field in animal husbandry.

Determination of the Heterogeneity of Intramuscular Fat and Visceral Adipose Tissue From Dezhou Donkey by Lipidomics and Transcriptomics Profiling.

Intramuscular fat (IMF) and visceral adipose tissue (VAT) are both lipids, but have significantly different deposition processes. Furthermore, the heterogeneity of lipid molecular characteristics and mechanisms is unclear. Accordingly, this study used non-targeted lipidomics and transcriptomics to analyze the lipid profiles and metabolism of longissimus dorsi muscle (LDM) and VAT from donkeys. A total of 1,146 and 1,134 lipids belonging to 18 subclasses were identified in LDM and VAT, respectively, with LDM having higher glycerophospholipid (GP) and lower glycerolipid (GL) contents. Polyunsaturated fatty acids (PUFAs) were distributed preferentially at the sn-1 positions in triglycerides (TGs), and sn-2 positions in phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The percentage PUFA content in TGs was significantly lower in LDM than in VAT, while the opposite trend was observed for PUFAs in PC and PE. A total of 110 different lipid molecules (72 downregulated and 38 upregulated) were identified in LDM compared with VAT, of which 11 were considered potential lipid markers. These different lipids were involved in 17 metabolic pathways, including GL and GP metabolisms. Of the 578 differentially expressed genes screened, 311 were downregulated and 267 were upregulated in LDM compared with VAT. Enriched ontology analysis of the differentially expressed genes mainly involved sphingolipid signaling pathways, and GP, GL, and sphingolipid metabolisms. Overall, lipidomics and transcriptomics indicated differences in lipid profiles and metabolism in LDM and VAT, providing new perspectives for the study of heterogeneity in IMF and VAT.