Junyao Xiao

MicroRNAs (miRNAs) are small non-coding RNAs (18-26 nucleotides) that regulate gene expression by interacting with target mRNAs, affecting various physiological and pathological processes. miRTarBase, a database of experimentally validated miRNA-target interactions (MTIs), now features over 3 817 550 validated MTIs from 13 690 articles, significantly expanding its previous version. The updated database includes miRNA interactions with therapeutic agents, revealing roles in drug resistance and therapeutic strategies. It also highlights miRNAs as predictive, safety and monitoring biomarkers for toxicity assessment, clinical treatment guidance and therapeutic optimization. The expansion of miRNA-mRNA and miRNA-miRNA networks allows the identification of key regulatory genes and co-regulatory miRNAs, providing deeper insights into miRNA functions and critical target genes. Information on oxidized miRNA sequences has been added, shedding light on how oxidative modifications influence miRNA targeting and regulation. The integration of the LLAMA3 model into the NLP pipeline, alongside prompt engineering, enables the efficient identification of MTIs and miRNA-disease associations without large training datasets. An updated data integration and a redesigned user interface enhance accessibility, reinforcing miRTarBase as an essential resource for molecular oncology, drug development and related fields. The updated miRTarBase is available at https://mirtarbase.cuhk.edu.cn/∼miRTarBase/miRTarBase_2025.

This study investigated the effect of dietary Mn supplementation on eggshell quality, ultrastructure, glycosaminoglycan (GAG), and uronic acid content, and mRNA and protein expression of Galβ1,3-glucuronosyltransferase (GlcAT-I). A total of 216 layers (Hy-Line Grey) at age of 50 wk were divided into 3 groups. In the first 8 wk of the 12-wk feeding trial, all groups were fed a basal diet that met all layer nutrient requirements except for Mn. In the last 4 wk, each group was fed 1 of 3 diets supplemented with Mn levels at 0, 25, or 100 mg Mn/kg. Dietary Mn deficiency did not affect the egg performance of layers. Dietary Mn supplementation significantly improved the breaking strength, thickness, and fracture toughness of eggshells (P < 0.05). In photographs of eggshell ultrastructure, the size of mammillary cones and cracks in the outer surface were decreased by dietary Mn supplementation. The contents of GAG and uronic acids in eggshell membrane were significantly increased by dietary Mn addition (P < 0.05). This result was further confirmed by increased mRNA expression and protein expression of GlcAT-I when Mn was added to the diet. This study suggests that dietary Mn supplementation can improve eggshell quality by enhancing the GAG and uronic acid synthesis in the eggshell glands, which can affect the ultrastructure of eggshells.

This study was aimed at investigating the bioefficacy of organic compared with inorganic manganese (Mn) for eggshell quality. An amino acid-Mn complex or Mn sulfate monohydrate was used as the organic or inorganic Mn source. A total of six hundred forty-eight 50-wk-old layers (Hy-Line Brown) were divided into 9 groups; each group consisted of 6 replicates with 12 layers each. The feeding trial lasted 12 wk. During the first 4 wk of the feeding trial, the groups were fed a basal diet, which met the nutrient requirements of the layers, except for Mn. During the following 8 wk, 9 levels of Mn (inorganic Mn: 0, 25, 50, 100, and 200 mg/kg; organic Mn: 25, 50, 100, and 200 mg/kg) were used to supplement, respectively, in the basal diet on an equimolar basis. An exponential regression model was applied to calculate the bioefficacy of organic Mn compared with the inorganic Mn. Dietary supplementation with either organic or inorganic Mn did not influence egg production and feed efficiency of (P > 0.05), and eggshell quality did not exhibit a significant response to dietary supplementation with Mn sources at 56 and 58 wk (P > 0.05). Dietary supplementation with either organic Mn or inorganic Mn significantly enhanced the thickness, breaking strength, and elastic modulus of the eggshells compared with the control group at the end of 62 wk (P < 0.05). At the end of 62 wk, the bioefficacy of organic Mn was 357% (shell thickness), 406% (breaking strength), 458% (elastic modulus), and 470% (eggshell Mn), as efficacious as inorganic Mn at equimolar levels. This study suggests that organic Mn enhances eggshell quality in aged laying hens compared with inorganic Mn.

Background: XueBiJing injection (XBJ) is renowned for its multi-target pharmacological effects, including immunomodulatory, antithrombotic, and antioxidant activities, offering potential therapeutic benefits for patients with severe infections such as sepsis and Coronavirus disease 2019 (COVID-19). Despite its clinical effectiveness, the molecular targets and mechanisms of XBJ remain unclear, warranting further investigation. Purpose: This study aimed to identify the key bioactive compounds in XBJ and elucidate their molecular targets and mechanisms. Methods: The zebrafish model was first used to evaluate the anti-inflammatory and antioxidant effects of XBJ, and the differentially expressed genes (DEGs) were identified by RNA sequencing and network analysis. Network pharmacology was used to analyze the relationship between bioactive compounds and molecular targets, and molecular docking and kinetic simulation were used to explore the target binding ability of key compounds. Cellular Thermal Shift Assay-Western Blot (CETSA-WB) and Surface Plasmon Resonance (SPR) further verified the interaction between compounds and targets; finally, the key pathways were confirmed by gene silencing experiments. Results: The zebrafish model results reveal that XBJ significantly reduced neutrophil and macrophage counts in a dose-dependent manner, emphasizing its potent anti-inflammatory effects. A transcriptomic analysis highlighted the differential expression of key genes in the KEAP1/NRF2 pathway, including HMOX1, SLC7A11, NQO1, and TXNRD1. A network analysis further pinpointed KEAP1 as a central molecular target, with tanshinone IIA, baicalein, and luteolin identified as key active compounds modulating this pathway. Among these, tanshinone IIA and baicalein exhibited strong binding interactions with KEAP1, which were confirmed through molecular docking and kinetic simulations. Further validation showed that baicalein directly targets KEAP1, as demonstrated by CETSA-WB and SPR analysis. Additionally, the gene silencing experiments of KEAP1 and NRF2 reinforced their crucial roles in activating the KEAP1/NRF2 pathway. Conclusion: These findings collectively establish baicalein as a critical bioactive compound in XBJ, driving its antioxidant and anti-inflammatory effects via KEAP1/NRF2 pathway activation through direct binding to KEAP1, providing new insights into the mechanism of action of XBJ.

Jatropha curcas oil (JCO) is non-edible due to the content of phorbolesters (PEs) which are very toxic. The aim of this study was to evaluate the potential of JCO, treated by ultraviolet irradiation combined with ethanol washing, as an edible oil. The results showed that PEs can be significantly decreased by 100% (p &lt; 0.05), but the treatments produced no significant changes (p &lt; 0.05) in the fatty acids composition (FAC) and triacylglycerols (TAGs) in the detoxified Jatropha curcas oil (DJCO). In addition, the quality of DJCO was improved with enhanced DPPH radical scavenging. Therefore, DJCO with good quality will become a good resource for edible oil.