Maize, one of the most widely cultivated crops globally, is highly susceptible to mycotoxin contamination. In this study, an endophytic strain Pseudomonas sp. HP-1, isolated from Peganum harmala L., demonstrated significant biocontrol potential. The culture extract of Pseudomonas sp. HP-1 (PHE) exhibited strong antifungal activity, with inhibition zones of 40.07 ± 0.21 mm against Penicillium italicum, 29.71 ± 0.25 mm against Aspergillus niger, and 23.10 ± 0.44 mm against A. flavus, along with notable antibacterial activity against Staphylococcus aureus (22.43 ± 0.55 mm). At a concentration of 16 mg/mL, PHE almost completely inhibited the mycelial growth of A. flavus. The antifungal mechanism of PHE was investigated through scanning electron microscopy (SEM) and propidium iodide (PI) staining analysis, which demonstrated that antifungal activity is primarily through the disruption of cellular membrane integrity. Furthermore, PHE significantly reduced the incidence of A. flavus contamination in agroecological maize seeds during storage, and treated PHE showed superior antifungal efficacy compared to non-treated PHE, highlighting its potential as an effective antifungal agent for seed protection. Through one- and two-dimensional NMR and MS analyses, the primary active compound of PHE was identified as 1-phenazinecarboxylic acid. These findings indicate that PHE can be utilized as a sustainable antifungal agent for protecting maize seeds against mycotoxin-producing fungi.

The introduction of cyano groups into aza-heterocyclic compounds plays a pivotal role in accessing diverse derivatives that are essential for the development of natural products, pharmaceuticals, and agrochemicals. Herein, we report a unified strategy for the direct ortho-C-H cyanation of a broad range of heterocyclic N-oxides, including pyridine, quinoline, isoquinoline, and pyrimidine derivatives. This transformation proceeds under mild conditions without the need for external activating agents or catalysts, and has been successfully applied to structurally complex, biologically relevant molecules. Compared to existing methodologies, our approach offers several distinct advantages: the use of non-prefunctionalized heteroarene substrates, environmentally benign reaction solvents, operational simplicity, broad substrate scope, and high efficiency in generating diverse ortho-cyanated heterocyclic compounds. Moreover, the method demonstrates considerable potential for scalable synthesis.

Glutathione peroxidase 4 (GPX4) is canonically viewed as the primary suppressor of ferroptosis, yet its role in the tumor microenvironment (TME) extends far beyond antioxidant catalysis to encompass immuno-metabolic regulation. In this review, we synthesize recent advances in enzymology, immunology, and cancer metabolism to propose a “lipid peroxidation threshold” framework, wherein GPX4 sets cell-type-specific thresholds that determine susceptibility to ferroptosis across tumor cells, CD8⁺ T cells, dendritic cells (DCs), and myeloid populations. We discuss how these thresholds are dynamically adjusted by post-translational modifications, nutrient competition and intercellular feedback loops, resulting in significant spatial heterogeneity between the tumor core and the tumor invasive front. There is a current selectivity paradox in GPX4 inhibitors, as well as resistance through nuclear factor erythroid 2-related factor 2 (Nrf2) and ferroptosis suppressor protein 1 (FSP1) that restricts the efficacy of GPX4 inhibitors as monotherapy. We focus on rational combination approaches: GPX4 modulation with immune checkpoint blockade (ICB), chemotherapy, and targeting myeloid-derived suppressor cells (MDSCs); and the pressing need for predictive biomarkers and single-cell spatial profiling. We conclude that successful clinical translation requires moving beyond indiscriminate GPX4 inhibition toward precision “threshold engineering” that selectively lowers tumor lipid peroxidation thresholds while sparing immune cells.