Functional FOXA1 targeting is mostly unique to each of the four human cancer cell lines HepG2, LNCaP, MCF7, and T47D.

Spider venom has been found to show its anticancer activity in a variety of human malignancies, including lung cancer. In this study, we investigated the anti-cancer peptide toxin LVTX-8, with linear amphipathic alpha-helical conformation, designed and synthesized from the cDNA library of spider Lycosa vittata. Multiple cellular methods, such as CCK-8 assay, flow cytometry, colony formation assay, Transwell invasion and migration assay, were performed to detect peptide-induced cell growth inhibition and anti-metastasis in lung cancer cells. Our results demonstrated that LVTX-8 displayed strong cytotoxicity and anti-metastasis towards lung cancer in vitro. Furthermore, LVTX-8 could suppress the growth and metastasis of lung cancer cells (A549 and H460) in nude mouse models. Transcriptomics, integrated with multiple bioinformatics analysis, suggested that the molecular basis of the LVTX-8-mediated inhibition of cancer cell growth and metastasis manifested in two aspects: Firstly, it could restrain the activity of cancer cell division and migration through the functional pathways, including “p53 hypoxia pathway” and “integrin signaling”. Secondly, it could regulate the expression level of apoptotic-related proteins, which may account for programmed apoptosis of cancer cells. Taken together, as an anticancer peptide with high efficiency and acceptable specificity, LVTX-8 may become a potential precursor of a therapeutic agent for lung cancer in the future.

Background: Ferroptosis is a form of programmed cell death triggered by iron-dependent lipid peroxidation, characterized by iron accumulation and elevated reactive oxygen species (ROS), leading to cell membrane damage. It is associated with a variety of diseases. However, the cellular and molecular links between ferroptosis, immune inflammation, and the brain-peripheral blood axis in Alzheimer’s disease (AD) remain unclear. Methods: We integrated bulk RNA-seq data from AD brain tissue and peripheral blood and refined the screening of AD candidate genes through differential gene expression analysis, weighted gene co-expression network analysis (WGCNA), and other approaches. Additionally, we analyzed single-cell RNA-seq (scRNA-seq) data from AD patients’ brain tissue and peripheral blood, combined with scRNA-seq data from experimental autoimmune encephalomyelitis (EAE) mouse brain tissue. This enabled us to explore AD-related molecular mechanisms from a cell-type-specific perspective. Finally, candidate genes were validated in ferroptosis models using reverse transcription quantitative PCR (RT-qPCR) and immunofluorescence methods. Results: Bulk RNA-seq analysis identified SLC11A1, an inflammatory gene associated with AD. Single-cell RNA-seq analysis further revealed that SLC11A1 expression was significantly elevated in the pro-inflammatory (M1-type) microglia and peripheral blood monocytes in AD. Moreover, we identified a microglial subpopulation in AD M1-type microglia that was highly associated with ferroptosis. This subpopulation simultaneously expressed characteristic markers of peripheral blood monocytes, suggesting that these cells may originate from peripheral blood monocytes, thereby triggering neuroinflammation through the ferroptosis pathway. Cell experiments confirmed that SLC11A1 was significantly upregulated in inflammatory microglia induced by ferroptosis. Conclusion: This study reveals the key role of SLC11A1 in AD, particularly in the context of ferroptosis and immune inflammation. It provides a novel molecular mechanistic perspective and offers potential targets for future therapeutic strategies.

This study revealed the heterogeneity of E. coli strains from pigs, including two strains studied by both in silico and wet experiments in detail and 14 strains studied by bioinformatics analysis. E. coli Y18J may improve the adaptability of pigs toward disease resistance through the production of colicins B and M. Our findings could shed light on the pathogenic and harmless roles of E. coli in modern animal husbandry, leading to a better understanding of intestinal-microbe–pathogen interactions in the course of evolution.

Phosphorus is a crucial nutrient for plant growth, but only a limited quantity is typically accessible in the soil for plants to absorb directly. Phosphate-solubilizing bacteria (PSB) can convert inorganic phosphorus compounds into forms that are more readily usable for plant nutrition. Our previous research has verified the function of Pediococcus pentosaceus PSM16 in degrading phytic acid. On this basis, we further explored the phosphorus-solubilizing capacity of PSM16 and evaluated its potential for practical application in this study. The results indicated that PSM16 significantly enhanced phosphorus utilization, not only enriching the environment with bioavailable phosphorus but also lowering the environmental pH and conductivity. These changes are instrumental in enhancing soil fertility, providing favorable conditions for plant growth, and stimulating seed germination. Through whole-genome sequencing of PSM16, we have identified key genes associated with the production of acid phosphatase. Specifically, the genes of GM000834, GM000917, GM000925, and GM000974 are implicated in PSM16’s phosphorus solubilization function, likely through the production of phosphatase enzymes. Moreover, we have discovered that the phosphatases T.fus-QOS58989.1, A.cae-WP_156200763, M.the-SNW17984, N.gly-GGP12115, T.chr-SDQ48339.1, and T.chr-SDQ90039.1 are homologous to the aforementioned proteins and are present in compost, as confirmed by our informatics analysis. This presence in compost suggests their potential for real-world agricultural applications. This research presents promising candidate strains for the development of phosphorus-degrading bacterial agents, which could increase the efficiency of phosphorus fertilizers and contribute to sustainable agricultural practices. This strategy is not only effective but also environmentally benign and cost-effective, offering a valuable contribution to the field of agricultural biotechnology. IMPORTANCE: This study sheds light on the transformative power of the PSM16 strain, a paragon of phosphorus solubilization that adeptly converts inert phosphorus into a form that is readily absorbed by plants. In this way, it not only elevates the levels of available phosphorus in the environment but also enriches the soil fertility, supporting the healthy growth of plants. The strategic application of PSM16 in tandem with phosphorus fertilizers promises to enhance the utilization rates of these fertilizers, reinforcing sustainable agricultural initiatives and alleviating the environmental pressures caused by excessive application. In addition, the study has uncovered a trove of strains that hold promise for the development of safe dephosphorylating bacterial agents. These agents are poised to deliver an economical, efficient, and eco-friendly alternative, encapsulating a commitment to agricultural advancement that is both responsible and resourceful.