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Deoxynivalenol (DON) is a prevalent toxin causing severe liver damage through hepatocellular oxidative stress. However, the underlying mechanisms and effective therapeutic approaches remain unknown. Here, the unique role of the xenobiotic metabolism factor pregnane X receptor (PXR) in mediating DON‐induced hepatocellular oxidative stress is investigated. Treatment with the PXR agonist 3‐indole‐propionic acid (IPA) alleviates DON‐induced oxidative stress and liver injury both in vitro and in vivo. Mechanistically, it is discovered for the first time that PXR agonist IPA directly transactivates the m6A demethylase FTO expression, leading to site‐specific demethylation and decreased abundance of YTHDC1‐bound Malat1 lncRNA at single‐nucleotide resolution. The diminished m6A modification of Malat1 lncRNA reduces its stability and augments antioxidant pathways governed by NRF2, consequently mitigating DON‐induced liver injury. Furthermore, Malat1 knockout mice exhibit decreased DON‐induced liver injury, emphasizing the role of Malat1 lncRNA in oxidative stress. Collectively, the findings establish that PXR‐mediated m6A‐dependent Malat1 lncRNA expression determines hepatocyte oxidative stress via m6A demethylase FTO, providing valuable insights into the potential mechanisms underlying DON‐induced liver injury and offers potential therapeutic strategies for its treatment. [ABSTRACT FROM AUTHOR]

A kind of adsorbent (Hydrogel-I) derived from sodium alginate and modified alkaline lignin (MAL) has been proved to possess a good adsorption performance for Pb(II)-loaded wastewater based on batch experiments. However, practical removal of Pb(II)-loaded-wastewater is a continuous and dynamic process. Herein, Hydrogel-I was further evaluated by packing it into a fixed-bed column. The breakthrough curves were established under different inflow rates (0.159–0.318 L/min), inflow directions (down-inflow mode and top-inflow mode), initial concentrations (5–20 mg/L) of Pb(II), and bed depths (20–60 cm). The results indicated that the slower inflow rate (0.159 L/min), down-inflow mode, lower initial concentration (5 mg/L), and higher bed depth (60 cm) prolonged breakthrough times (tb) and saturation times (ts). Compared to the top-inflow mode, the down-inflow mode guaranteed enough contact between Hydrogel-I and Pb(II). The values of adsorption capacity at tb, ts, and the removal efficiency under the down-inflow mode were higher than that under top-inflow mode by 2.33, 0.78, and 0.07 times, respectively. Hydrogel-I beads exhibited better adsorption performance than other adsorbents by comparing the rate constant (kAB) and the adsorption capacity (N0). The kAB and N0 of Hydrogel-I beads were calculated to be 0.0034 L/(mg·min−1) and 678 mg/L. Hydrogel-I beads showed good regeneration ability in a three-adsorption-desorption cycle. Meanwhile, FT-IR analysis showed that the groups of –NH/–NH2, C=S, and C–S were proved to be the adsorption sites. This study could prove valuable insight into the practical application of Hydrogel-I for dynamic removal of Pb(II) in an inflow-through column. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON) is a prevalent toxin causing severe liver damage through hepatocellular oxidative stress. However, the underlying mechanisms and effective therapeutic approaches remain unknown. Here, the unique role of the xenobiotic metabolism factor pregnane X receptor (PXR) in mediating DON-induced hepatocellular oxidative stress is investigated. Treatment with the PXR agonist 3-indole-propionic acid (IPA) alleviates DON-induced oxidative stress and liver injury both in vitro and in vivo. Mechanistically, it is discovered for the first time that PXR agonist IPA directly transactivates the m 6 A demethylase FTO expression, leading to site-specific demethylation and decreased abundance of YTHDC1-bound Malat1 lncRNA at single-nucleotide resolution. The diminished m 6 A modification of Malat1 lncRNA reduces its stability and augments antioxidant pathways governed by NRF2, consequently mitigating DON-induced liver injury. Furthermore, Malat1 knockout mice exhibit decreased DON-induced liver injury, emphasizing the role of Malat1 lncRNA in oxidative stress. Collectively, the findings establish that PXR-mediated m 6 A-dependent Malat1 lncRNA expression determines hepatocyte oxidative stress via m 6 A demethylase FTO, providing valuable insights into the potential mechanisms underlying DON-induced liver injury and offers potential therapeutic strategies for its treatment., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Bile acids (BAs) are synthesized by liver, then gut microbes embellish primary BAs into secondary BAs with diverse and biological functions. Over the past few decades, amounts of evidences demonstrated the importance of gut microbes in BA metabolism. There is also significant evidence that BAs are regarded as cell signals in gut-liver, gut-brain, and gut-testis axis. Moreover, the interaction between BAs and gut microbes plays a key role not only in the absorption and metabolism of nutrients, but the regulation of immune function. Herein, we collected the major information of the BA metabolism-related bacteria, nutrients, and cell signals, focused on the possible molecular mechanisms by "Microbes-Bile acids" crosstalk, highlighted the gut-liver, gut-brain, and gut-testis axis, and discussed the possibility and application of the regulation of BA metabolism by nutrients.