8 million ZINC15 compounds against βH-NOX domain. The docked ligands were further probed in terms of contact footprint and pose reassessment through clustering analysis and PLANTS docking, respectively. Subsequently, energy-based AMBER rescoring of top 100 low-energy complexes, per-residue energy decomposition analysis, and ADME-Tox analysis yielded the top three compounds i.e. ZINC000098973660, ZINC001354120371, and ZINC000096022607. The impact of three selected ligands on the internal structural dynamics of the βH-NOX domain was also investigated through molecular dynamics simulations. The study revealed potential electrostatic interactions for better conformational dialogue between βH-NOX domain and allosteric ligands that are critical for the activation of hsGC as compared to the reference compound.Either in clinical study or biomedical research, it is a common practice to combine multiple biomarkers to improve the overall diagnostic performance. Despite the fact there exist a large number of statistical methods for biomarker combination under binary classification, research on this topic under multi-class setting is sparse. The overall diagnostic accuracy, i.e. the sum of correct classification rates, directly measures the classification accuracy of the combined biomarkers. Hence the overall accuracy can serve as an important objective function for biomarker combination, especially when the combined biomarkers are used for the purpose of making medical diagnosis. In this paper, we address the problem of combining multiple biomarkers to directly maximize the overall diagnostic accuracy by presenting several grid search methods and derivation-based methods. A comprehensive simulation study was conducted to compare the performances of these methods. An ovarian cancer data set is analyzed in the end.Maternal attachment security is an important predictor of caregiving . However, little is known regarding the neurobiological mechanisms by which attachment influences processing of infant cues, a critical component of caregiving. We examined whether attachment security, measured by the Adult Attachment Interview, might relate to neural responses to infant cues using event-related potentials. Secure (n=35) and insecure (n=24) mothers viewed photographs of infant faces and heard recordings of infant vocalizations while electroencephalography was recorded. We examined initial processing of infant faces (N170) and cries (N100), and attentional allocation to infant faces and cries (P300). Secure mothers were significantly faster than insecure mothers to orient to infant cries (N100), structurally encode their own infant's face (N170), and attend to infant faces (P300). These differences may elucidate mechanisms underlying how attachment may shape neural processing of infant cues and highlight the use ofsocial neuroscientific approaches in examining clinically relevant aspects of attachment.The hallmark of the Alzheimer's disease (AD) is the accumulation of aggregated, misfolded proteins. The cause for this accumulation is increased production of misfolded proteins and impaired clearance of them. Amyloid aggregation and tau hyperphosphorylation are the two proteinopathies which accomplish deprivation of cell and tissue hemostasis during neuropathological process of the AD, as a result of which progressive neuronal degeneration and the loss of cognitive functions. p38 mitogen-activated protein kinase (p38 MAPK) has been implicated in both the events associated with AD tau protein phosphorylation and inflammation. p38α MAPK pathway is activated by a dual phosphorylation at Thr180 and Tyr182 residues. Clinical and preclinical evidence implicates the stress related kinase p38α MAPK as a potential neurotherapeutic target. Drug design of p38α MAPK inhibitors is mainly focused on small molecules that compete for Adenosine triphosphate in the catalytic site. Here we have carried out the synthesis of phenyl sulfonamide derivatives Sulfo (I) and Sulfo (II). Crystal structures of Sulfo (I) and Sulfo (II) were solved by direct methods using SHELXS-97. Sulfo (I) and Sulfo (II) have Rint values of 0.0283 and 0.0660, respectively, indicating good quality of crystals and investigated their ability against p38α MAPK. Docking studies revealed that the Sulfo (I) had better binding affinity (-62.24 kcal/mol) as compared to Sulfo (II) and cocrystal having binding affinity of -54.61 kcal/mol and -59.84 kcal/mol, respectively. Molecular dynamics simulation studies of Sulfo (I) and cocrystal of p38α MAPK suggest that during the course of 30 ns simulation run, compound Sulfo (I) attained stability, substantiating the consistency of its binding to p38α MAPK compared to cocrystal. Binding free energy analysis suggests that the compound Sulfo (I) is better than the cocrystal. Thus, this study corroborates the therapeutic potential of synthesized Sulfo (I) in combatting AD.Communicated by Ramaswamy H. Sarma. has different roles in multiple types of cancers and participates in various molecular mechanisms. However, the prognostic value of in patients with hepatocellular carcinoma (HCC) still remains unclear. We carried the study to evaluate the prognostic value and identified underlying molecular mechanisms in HCC. Firstly, the association of expression and clinicopathological parameters was evaluated by in GSE14520. Next, expression in HCC was performed using GSE14520, GSE36376, GSE76427 and The Cancer Genome Atlas (TCGA) profile. GDC0449 Furthermore, Kaplan-Meier analysis, Univariate and Multivariate Cox regression analysis, subgroup analysis was performed to evaluate the prognostic value in HCC. Finally, GO enrichment analysis, gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) were performed to revealed underlying molecular mechanisms. The expression of was positively correlated with the development of HCC. Next, high expression was significantly associated with poorer survival (all < 0.05) and the impact of on all overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), disease specific survival (DSS) and progression free interval (PFI) was specific for HCC among other 29 cancer types. Subgroup analysis showed that overexpression was significantly associated with poorer OS in patients with HCC. Finally, might participate in the status conversion from metabolic-dominant to extracellular matrix-dominant, and the activation of ECM-related biological process might contribute to high higher mortality risk for patients with HCC. may play an important role in the progression of HCC, and may be considered as a novel and effective biomarker for predicting prognosis for patients with HCC.ADAMTS5 may play an important role in the progression of HCC, and may be considered as a novel and effective biomarker for predicting prognosis for patients with HCC.