Lanoteplase

We report a novel mechanism in adventitious root formation, where a non-canonical auxin response factor, RpARF12, uniquely integrates continuous light (CL) signals with auxin pathways to regulate adventitious root formation in Robinia pseudoacacia L. (black locust). Unlike typical ARFs, the RpARF12 lacks the C-terminal dimerization (CTD) domain, suggesting its function through auxin-independent regulatory pathways. Our comprehensive analysis revealed that RpARF12 expression is significantly induced by CL and plays a crucial role in adventitious root formation under these conditions. Heterologous transformation of RpARF12 into model plants, including Arabidopsis thaliana, Nicotiana tabacum, and Populus alba × P. glandulosa (poplar 84K), significantly promoted adventitious root formation, particularly under CL. Additionally, the application of exogenous auxin further increased the number and length of roots in RpARF12-overexpressed A. thaliana plants under CL by 1.60 and 1.37 times, respectively, compared to wild-type plants. The auxin polar transport inhibitor NPA decreased root formation in the RpARF12-overexpressed A. thaliana plants under CL conditions. This study provides valuable insights into the regulatory role of photoperiod, specifically CL, on adventitious root formation and highlights the important role of RpARF12 in this process.

Poly (ADP-ribose) polymerase-1 (PARP-1) is a key enzyme in the base excision repair pathway, crucial for maintaining genomic stability by repairing DNA breaks. In cancers with mutations in DNA repair genes, such as BRCA1 and BRCA2, PARP-1 activity becomes essential for tumor cell survival, making it a promising target for therapeutic intervention. This study employs QSAR modeling, virtual screening, and molecular dynamics (MD) simulations to identify potential PARP-1 inhibitors. A dataset of inhibitors was analyzed using 12 molecular fingerprint descriptors to develop robust QSAR models, with the optimal model based on the CDK descriptor achieving R² = 0.96, Q²_CV = 0.78, and Q²_Ext = 0.80. The model was applied to virtually screen three chemical libraries-ZINC, FDA, and NPA-identifying promising candidates for PARP-1 inhibition. Molecular docking revealed that compounds ZINC13132446, Z2037280227, and NPC193377 have strong binding affinity for the PARP-1 active site. MD simulations and MM-PBSA confirmed the stability of these complexes, with Z2037280227 and NPC193377 exhibiting the most stable interactions. These results underscore the potential of targeting PARP-1 as a therapeutic strategy for cancers with homologous recombination deficiencies, including prostate, breast, and ovarian cancer, particularly in patients with DNA repair deficiencies.