Hydrolysable tannin improves growth performance and liver health of largemouth bass (Micropterus salmoides) fed high soybean meal diets.

This study provided evidence that the inclusion of hydrolysable tannin (HT) in high soybean meal (SBM) diets improved growth performance and glycolipid metabolism of largemouth bass (Micropterus salmoides). In vivo, various levels of HT were added to high SBM diets and fed to largemouth bass (initial weight: 6.00 ± 0.03 g) for 56 days. Results showed that a high level of SBM led to the reduction in growth performance, as evidenced by decreased weight gain rate and impaired hepatic function. Dietary supplementation with HT (1.0 g/kg) improved growth performance of largemouth bass, accompanied by the enhancements in hepatic antioxidant capacity and glycolipid metabolism. In vitro, HT facilitated glucose utilization in hepatocytes and positively influenced the modulation of crucial genes within the PI3K/Akt signaling pathway. Conversely, administration of LY294002 (a PI3K inhibitor) reversed the detrimental effects observed in hepatocytes exposed to high glucose levels. Overall, incorporating HT (1.0 g/kg) into the diet enhanced liver health and improved the absorption and utilization of SBM in largemouth bass, potentially achieved through modulation of the PI3K/Akt signaling pathway.

Sulfated disaccharide protects membrane and DNA damages from arginine-rich dipeptide repeats in ALS.

Hexanucleotide repeat expansion in C9ORF72 (C9) is the most prevalent mutation among amyotrophic lateral sclerosis (ALS) patients. The patients carry over ~30 to hundreds or thousands of repeats translated to dipeptide repeats (DPRs) where poly-glycine-arginine (GR) and poly-proline-arginine (PR) are most toxic. The structure-function relationship is still unknown. Here, we examined the minimal neurotoxic repeat number of poly-GR and found that extension of the repeat number led to a loose helical structure disrupting plasma and nuclear membrane. Poly-GR/PR bound to nucleotides and interfered with transcription. We screened and identified a sulfated disaccharide that bound to poly-GR/PR and rescued poly-GR/PR-induced toxicity in neuroblastoma and C9-ALS-iPSC-derived motor neurons. The compound rescued the shortened life span and defective locomotion in poly-GR/PR expressing Drosophila model and improved motor behavior in poly-GR-injected mouse model. Overall, our results reveal structural and toxicity mechanisms for poly-GR/PR and facilitate therapeutic development for C9-ALS.

Application of bovine bone meal and oyster shell meal to heavy metals polluted soil: Vegetable safety and bacterial community.

The development of efficient, environmentally friendly soil amendments is necessary in order to minimize the risk of metal contaminants (Cd, Pb, Cu, and Zn) to the soil ecosystem. As soil amendments, bovine bone meal (BM) and oyster shell meal (OS) reduced the mobility and bioavailability of metals primarily by increasing soil pH. Soil geochemical properties (pH, EC, CEC, Ca, P, and K) after amendment supplementation were more likely to affect metal migration than enzyme activity. Furthermore, BM and OS were found to suppress the Cd and Pb uptake by water spinach, keeping them below international standards for safe utilization. The protein and sugar content and peroxidase (POD) activity showed a significant negative correlation with the amount of metal in water spinach, whereas superoxide dismutase (SOD), ascorbate peroxidase (APX) activities and malondialdehyde (MDA) content exhibited a positive correlation with metal content in water spinach. We also found that BM and OS had less perturbation to phylum-level and genus-level bacterial composition during the remediation of heavy metals contaminated soil. Based on the above, we assume that BM and OS are eco-friendly soil amendments, which could improve soil nutrients contents, stabilize heavy metals and regulate bacterial community structure. Our research contributes to resource utilization of waste and holds promise for widespread application in current agricultural systems.

Remediation of Cd-, Pb-, Cu-, and Zn-contaminated soil using cow bone meal and oyster shell meal.

To understand the environmental friendliness and high efficiency of organic materials during remediating soil polluted by heavy metals by assessing the feedback of soil ecosystems after organic materials were put into polluted soil. Incubation research was undertaken to examine the impact of amendments ranging from 0.1% to 3.0% (w/w), including single cow bone meal (BM), single oyster shell meal (OS), and a composite of 50% BM mixed with 50% OS (BO) on soil biochemical properties. The findings revealed that the implementation of BM and OS increased soil pH, the content of certain nutrients, and the activities of catalase (S-CAT), and urease (S-UE) while decreasing the availability of Cd, Pb, Cu, and Zn. Overall, the immobilization effect on Cd and Zn after a 108-day incubation was ranked as follows: BM group > OS group ≥ BO group, and the order of the immobilization effect of Pb and Cu was OS group > BO group > BM group. In addition, the dominant bacterial community flora shifted toward alleviating the re-dissolution of metal ions from the soil and promoting nutrient recycling in soil within 108 days of cultivation. RNA analyses showed that the strongest determinants for microbial communities between BM application and OS application at the genus level were soil pH, CEC, and heavy metal (Cd, Pb). These results increase our understanding of the leaching performance of Cd, Pb, Cu and Zn and the evolution trend of microorganisms when organic amendments remediate heavy metal contaminated soil.

Ligand-dependent activation of EphA4 signaling regulates the proteolysis of amyloid precursor protein through a Lyn-mediated pathway.

Alzheimer's disease is the most common dementia afflicting the elderly in modern society. This disease arises from the neurotoxicity elicited by abnormal aggregates of amyloid-ß (Aß) protein. Such aggregates form through the cleavage of amyloid precursor protein (APP) by ß-secretase and the subsequent proteolysis of the APP C-terminal fragment (APP-ßCTF or C99) by γ-secretase to yield Aß and APP intracellular domain (AICD). Recent evidence suggests that C99 and AICD may exert harmful effects on cells, suggesting that the proteolytic products of APP, including Aß, C99, and AICD, could play a pivotal role in neuronal viability. Here, we demonstrate that ligand-activated EphA4 signaling governs the proteostasis of C99, AICD, and Aß, without significantly affecting γ-secretase activity. EphA4 induced accumulation of C99 and AICD through a Lyn-dependent pathway; activation of this pathway triggered phosphorylation of EphA4, resulting in positive feedback of C99 and AICD proteostasis. Inhibition of EphA4 by dasatinib, a receptor tyrosine kinase inhibitor, effectively suppressed C99 and AICD accumulation. Furthermore, EphA4 signaling controlled C99 and AICD proteolysis through the ubiquitin-proteasome system. In conclusion, we have identified an EphA4-Lyn pathway that is essential for the metabolism of APP and its proteolytic derivatives, thereby providing novel pharmacological targets for the development of anti-Aß therapeutics for AD.