were exhibited distinguish drug actions through the strong hydrogen bonding with the hot spots of the RBD. Besides, the 100 ns molecular dynamics simulation and free energy binding analysis showed the significant efficacy of luteolin to inhibit the infection of SARS-CoV-2.Communicated by Ramaswamy H. Sarma.Autophagosome formation requires PROPPIN/WIPI proteins and monophosphorylated phosphoinositides, such as phosphatidylinositol-3-phosphate (PtdIns3P) or PtdIns5P. This process occurs in association with mammalian endosomes, where the PROPPIN WIPI1 has additional, undefined roles in vesicular traffic. To explore whether these functions are interconnected, we dissected routes and subreactions of endosomal trafficking requiring WIPI1. WIPI1 specifically acts in the formation and fission of tubulo-vesicular endosomal transport carriers. This activity supports the PtdIns(3,5)P2-dependent transport of endosomal cargo toward the plasma membrane, Golgi, and lysosomes, suggesting a general role of WIPI1 in endosomal protein exit. Three features differentiate the endosomal and macroautophagic/autophagic activities of WIPI1 phosphoinositide binding site II, the requirement for PtdIns(3,5)P2, and bilayer deformation through a conserved amphipathic α-helix. Their inactivation preserves autophagy but leads to a strong enlargement of endosomes, which accumulate micrometer-long endosomal membrane tubules carrying cargo proteins. WIPI1 thus supports autophagy and protein exit from endosomes by different modes of action. We propose that the type of phosphoinositides occupying its two lipid binding sites, the most unusual feature of PROPPIN/WIPI family proteins, switches between these effector functions.AbbreviationsEGF epidermal growth factorEGFR epidermal growth factor receptorKD knockdownKO knockoutPtdIns3P phosphatidylinositol-3-phosphatePtdIns5P phosphatidylinositol-5-phosphatePtdIns(3,5)P2 phosphatidylinositol-3,5-bisphosphateTF transferrinTFRC transferrin receptorWT wildtype.In the present work, we report the synthesis, characterization of two cobalt complexes (1 and 2) and their HSA binding studies by multispectroscopic methods. see more Hirshfeld surfaces analysis and fingerprint plot analysis were carried out to identify intermolecular interactions viz., N-H···O, O-H···O and C-H···O linkages in crystal framework of the complexes. Density functional theory (DFT) studies were carried out to ascertain the electronic structure and molecular geometry of the complexes 1 and 2, and determine the localization of HOMO and LUMO in the complexes. A comparative in vitro interaction study of complex 1 and 2 with human serum albumin protein was carried out by employing UV-vis, fluorescence, circular dichroism, FTIR and molecular docking techniques. Interestingly, the HSA binding affinity of complex 2 was found to be more than complex 1 which was evidenced from the higher binding constant values owing to its strong hydrophobic topology. Further, a significant conformational change in microenvironment of HSA was noticed upon binding with complexes 1 and 2, nevertheless more perturbations were noticed in presence of complex 1. Molecular docking studies were carried out to validate the spectroscopic results and ascertain the preferential binding mode of complexes at the specific target site of HSA.Communicated by Ramaswamy H. Sarma.Research has shown that executive function (EF) skills are associated with resilience in preschoolers experiencing risk and adversity, but these studies have typically relied on large batteries of tasks to measure children's EF skills. There is a need for brief, reliable EF assessments that can be used in the field with diverse young children. The current study assessed the validity and test-retest reliability of two tablet-based EF tasks from the NIH Toolbox The Dimensional Change Card Sort (DCCS) and the Flanker Inhibitory Control and Attention Test, each with a developmental extension (Dext) that is triggered when a child struggles with the standardized versions. Dext versions include easier levels intended to improve task accessibility for younger and disadvantaged children. Eighty-six preschoolers residing in emergency housing participated in two study sessions about one week apart, completing tablet-based DCCS-Dext and Flanker-Dext tasks, along with a table-top EF task (Peg-Tapping) and measures of vocabulary and numeracy. The majority of participants triggered the Dext portion of the DCCS and almost half triggered the Dext portion of the Flanker, underscoring the need for extensions of the Toolbox EF tasks to lower the floor of these measures. The Dext EF measures were positively associated with Peg-Tapping, after controlling for age and vocabulary, indicating construct validity. They were also correlated with math achievement, suggesting criterion validity. DCCS-Dext and Flanker-Dext showed moderate test-retest reliability after one week. Together, these findings demonstrate the value of developmental extensions for assessing EF skills among children experiencing risk and adversity.It has become obvious that fluorinated drugs have a significant role in medicinal applications. In this study, the fluorination of mirtazapine antidepressant drug was investigated using density functional theory calculations. We found that the intramolecular hydrogen bonding and charge transfers of the mirtazapine drug were influenced by fluorine substitution. Our results also reveal that the fluorination altered the stability, solubility, and molecular polarity of the mirtazapine antidepressant drug. Moreover, our results show that the electronic spectra of fluorinated derivatives of the mirtazapine exhibit a red shift toward higher wavelengths compared to the original antidepressant drug. Our calculations show that the difference between G value of the gas and water (ΔG) of fluorinated derivatives of the mirtazapine drug was negative. We also found that the fluorination can increases the first hyperpolarizability of the mirtazapine antidepressant drug. Our results present an efficient strategy to improve the nonlinear optical responses of the antidepressant drugs. Consequently, the results of present study show that the fluorination of mirtazapine could be considered as a promising strategy to design antidepressant drugs with better pharmacological properties.Communicated by Ramaswamy H. Sarma.