Artificial Intelligence-Assisted Optimization of Antipigmentation Tyrosinase Inhibitors: De Novo Molecular Generation Based on a Low Activity Lead Compound.

Artificial intelligence (AI) de novo molecular generation is a highly promising strategy in the drug discovery, with deep reinforcement learning (RL) models emerging as powerful tools. This study introduces a fragment-by-fragment growth RL forward molecular generation and optimization strategy based on a low activity lead compound. This process integrates fragment growth-based reaction templates, while target docking and drug-likeness prediction were simultaneously performed. This comprehensive approach considers molecular similarity, internal diversity, synthesizability, and effectiveness, thereby enhancing the quality and efficiency of molecular generation. Finally, a series of tyrosinase inhibitors were generated and synthesized. Most compounds exhibited more improved activity than lead, with an optimal candidate compound surpassing the effects of kojic acid and demonstrating significant antipigmentation activity in a zebrafish model. Furthermore, metabolic stability studies indicated susceptibility to hepatic metabolism. The proposed AI structural optimization strategies will play a promising role in accelerating the drug discovery and improving traditional efficiency.

Comparison of Metabolites and Main Nutritional Components between Uncooked and Cooked Purple Rice.

Cooking can lead to varying degrees of nutrient loss in purple rice. For this investigation, two varieties of purple rice (YZN1 and YZ6) were chosen as the focal points to explore the metabolites associated with rice nutrition post cooking using nontargeted and targeted metabolomics techniques. The results showed that after cooking the two purple rice varieties, the contents of the flavonoids; OPC; TP; total antioxidant capacity; and K, Na, Fe, Mn, Zn, Cu, Ca, and Mg significantly decreased. Compared with YZN1U (YZN1 uncooked), the amino acid and mineral element contents in YZN1C (YZN1 cooked) decreased to varying degrees. After cooking YZ6, the contents of seven amino acids significantly decreased. Following the preparation of purple rice, the metabolites primarily engaged in the pathways of flavonoid synthesis and flavone and flavonol synthesis. Flavonoids, total antioxidant capacity, mineral elements, and amino acids showed a strong correlation with delphinidin and luteolin. The ROC analysis demonstrated that the value of the area under the curve for delphinidin and luteolin was 1 when comparing YZ6C (YZ6 cooked) and YZ6U (YZ6 uncooked), as well as YZN1C and YZN1U. Delphinidin and luteolin can be used as potential biomarkers of nutrient loss after cooking purple rice. This study holds significant implications for the balanced nutrition and healthy development of human dietary grains.

Blueberry fruit valorization and valuable constituents: A review.

Blueberry (Vaccinium spp.) is one of the five major healthy foods for humans and is recognized as the "king of the world fruit", which has attracted great interest in the phytogenic prebiotics market. Blueberry fruit is favored for its delicious taste and its various functional ingredients (organic acids, phenolics, minerals and vitamins) with multitherapeutic value (antioxidant, anti-inflammatory, anticancer, neuroprotective and vision improvement properties). However, fresh blueberries are highly perishable since they are vulnerable to mechanical damage and microbial decay, resulting in a short shelf life and inevitable subsequent economic losses. Due to the strong seasonal availability and limited storage period of blueberries, their derived bioactive products have emerged as functional foods. Novel food developments that are currently available include blueberry fruit juice, wine, vinegar, jam, dried fruit, pulp powder, colorant and flavoring additives used in cake, biscuit, bread, yogurt, and jelly. This review systematically describes the current status of blueberry fruit as bioactive ingredients and valuable food products with greater nutraceutical health potential of blueberries.

Biochar regulates bacterial-fungal diversity and associated enzymatic activity during sheep manure composting.

Aimed to evaluate the coexistence of bacterial and fungal diversity and their correlation with enzymatic activity in response to biochar. This study performed aerobic composting based on typical agricultural wastes of sheep manure with additive apple tree branch biochar at distinct concentration (0, 2.5, 5, 7.5, 10 and 12.5% corresponding from T1 to T6). The result demonstrated that appropriate amendment of biochar enriched bacterial diversity (1646-1686 OTUs) but interestingly decreased fungal diversity (542-630 OTUs) compared to control (1444 and 682 OTUs). Biochar addition enhanced all enzymatic activities and its correlation with bacterial was more complex than fungal community (786 and 359 connect edges). The dominant microbes comprised of Firmicutes (45.2-35.2%), Proteobacteria (14.0-17.5%), Basidiomycota (32.4-49.5%) and Ascomycota (11.3-37.5%) among all the treatments. Overall, biochar regulates the composting microenvironment by influencing the microbial diversity and associated enzymatic activities.

Grass waste utilization to alter aggregate-related carbon chemical composition and fungal community structure in apple orchard.

The grass-waste management model affects soil organic carbon (SOC) and the microorganism community structure; however, studies on the relationship between the fungal community structure and the SOC chemical component at the aggregate level are poor. Solid-state 13C NMR and 18 S rDNA methods were used to evaluate the relationship between the SOC chemical composition and fungal community abundance at the aggregate level. Grass mulching significantly increased the percentage of labile carbon O-alkyl C (5.19%-11.79%) and decreased the instability of SOC (1.38-0.69). Microaggregates contained higher alkyl C (33.77%) and lower aromatic C (18.31%), and the A/O-A ratio (1.03) was higher than that of macroaggregates (0.89-0.96). Ascomycota, Basidiomycota and Mortierellomycota dominated the fungal community at the phylum level, and their abundance increased after grass mulching. Microaggregates supported more microbial diversity and richness and were rich in the Ascomycota (36.69%-67.49%) phylum, while LM aggregates were rich in Basidiomycota (5.62%-39.84%). We proved that changes in the O-alkyl C, carbonyl C, aromatic C and alkyl C of SOC chemical components were closely connected to fungal community composition, which together explained the change in fungal composition by 63.81%-71.99% among aggregates. We concluded that alterations in the chemical form of organic carbon were closely related to a change in the soil fungal community. This connection has a positive impact on soil nutrient utilization and SOC conversion in fruit-grass composite ecosystems and promotes the understanding of the relationship between the soil microbial community and nutrient cycling during long-term grass waste utilization.