Density of states analysis also disclosed the prominent interactions of the biomolecules with the nano-TiO2 cluster. Decrease in band gaps on adsorption of the biomolecules was a pertinent phenomenon indicating the strong chemical interactions of the biomolecules with the nanoscopic TiO2 chosen for analysis in this study. The antidepressant medications that are currently prescribed to patients suffering from major depressive disorder (MDD) have limitations and as a result, there is an urgent need to increase the options that are available. A number of studies have found that natural polyphenols have neuroprotective properties and there is evidence to suggest that they modulate neurotransmitter systems. There are more than 200 phenolic compounds that have been identified in Olea europaea, many of which have not yet been investigated for their potential biological effects. In this study, in silico methods were used to screen the phenolic library from the OliveNet™ database and identify novel lead compounds for proteins implicated in the pathophysiology of MDD. The molecular docking results revealed that the monoamine oxidase enzyme isoforms (MAO-A/MAO-B) had binding specificities for certain phenolic subclasses. The lead ligands that were identified from these subclasses were positioned near the flavin adenine dinucleotide (FAD) cofactor, interacting in a similar manner as known inhibitors. In addition to the MAO enzymes, several phenolic compounds were docked to neurotransmitter transporters and postsynaptic receptors, as well as proteins involved in neuroinflammation, oxidative stress and the endocannabinoid system. Based on the binding affinity, position, orientation and interactions of the lead phenolic compounds identified in this study, it is predicted that they may have antidepressant properties. The results should be validated further using molecular dynamics (MD) simulations, as well as in vivo and in vitro techniques. Genomic instability can be life-threatening. The fine balance between error-free and mutagenic DNA repair pathways is essential for maintaining genome integrity. Recent advances in DNA double-strand break induction and detection techniques have allowed the investigation of DNA damage and repair in the context of the highly complex nuclear structure. These studies have revealed that the 3D genome folding, nuclear compartmentalization and cytoskeletal components control the spatial distribution of DNA lesions within the nuclear space and dictate their mode of repair. The fusion of two transcriptionally silent gametes, egg and sperm, generates a totipotent zygote that activates zygotic transcription to support further development. Although the molecular details of zygotic genome activation (ZGA) are not well understood in most species, an emerging concept is that one or more pioneer transcription factors trigger zygotic transcription. Concomitantly, extensive changes in 3D chromatin organization occur during development. In this review, we discuss recent advances in understanding when and how genome architecture emerges in early metazoan embryos, how the zygotic genome is activated, and how these events might be coordinated. We also highlight some of the unknowns that may be critical to address in the future. Inflammatory bowel disease could result in diarrhea and abdominal pain, as well as potential complications such as tissue fibrosis. The therapeutic effect of andrographolide sulfonate on acute murine experimental colitis induced by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) has been confirmed. In the study here, chronic colitis triggered by repeated intrarectal administration of TNBS was established and the effect of andrographolide sulfonate was examined. Repeated TNBS administration induced substantial mice death, which was significantly decreased by andrographolide sulfonate treatment. The elevation of inflammatory cytokines including IL-6, IL-17A, TNF-α as well as IFN-γ in colonic tissues levels were decreased after administration of andrographolide sulfonate. Next, CD4+ T cell and macrophage infiltration was found to descend. The subset of pathogenic CD4+ T cell subset including CD4+IFN-γ+ (Th1) and CD4+IL-17A+ (Th17) were also suppressed by andrographolide sulfonate. Further, the restrain of p38 and p65 activation were also observed after andrographolide sulfonate administration. Finally, TNBS-induced colonic epithelial damage as well as fibrosis were significantly mitigated by andrographolide sulfonate. Based on the results got here, we can make a conclusion that andrographolide sulfonate could decrease inflammation and epithelial damage as well as fibrosis thus ameliorating chronic colitis in mice. Our study suggest the possible use of andrographolide sulfonate for chronic colitis treatment in clinical. Melanomas represent the deadliest form of skin cancers. ISO-1 Due to the intricacy of tumorigenesis, it is emergent to find effective therapies for melanomas. Researches have proved that pimozide inhibits the growth of melanoma, but the limited curing effect needs to be further improved. Nowadays, tumor immunotherapy has been widely recognized as the sole therapy that can eradicate cancers. Cytosine-phosphate-guanine oligodeoxynucleotide (CpG ODN), TLR9 receptor agonist, can significantly enhance anti-tumor immune responses. This study explored the therapeutic effect of pimozide combined with CpG ODN on melanoma-bearing mice. The results showed that pimozide combined with CpG ODN effectively inhibited the growth of melanoma and prolonged the survival of melanoma-bearing mice, inhibited the expression of MMP2 and p-Stat5, increased the infiltration of CD4+ and CD8+ T cells in tumor, raised the ratios of CD4+, CD8+ T cells and NK cells. These all indicated that the combination treatment improved the anti-tumor effect of pimozide on mice. The anti-tumor mechanism might be attributed to cell apoptosis induction, invasion inhibition, and immune regulation. A more effective combination treatment concerning with pimozide is being under investigation. OBJECTIVE This study aimed to explore the prognostic value and functional role of Prolyl 4-Hydroxylase Subunit Alpha 3 (P4HA3) in head and neck squamous cell carcinoma. METHODS We downloaded the RNA-Seq dataset of head and neck squamous cell carcinoma for analyzing the expression of P4HA3 and determining its prognostic value. Head and neck squamous cell carcinoma cell lines CAL27 and FaDu were chose for gain- and loss-of-function of P4HA3 tests. mRNA and protein levels of P4HA3 in head and neck squamous cell carcinoma cells were tested by quantitative real-time PCR and western blot respectively. Cell counting Kit-8, clone formation assay, Transwell assay were used to determine the effect of P4HA3 on the proliferative, invasive and migratory capacities of head and neck squamous cell carcinoma cells. RESULTS Bioinformatics analysis showed that P4HA3 was up-regulated in head and neck squamous cell carcinoma tissues, and had an independent prognostic value for head and neck squamous cell carcinoma patients. The outcomes of gain- and loss-of-function tests illustrated that P4HA3 significantly boosted head and neck squamous cell carcinoma cell proliferative, invasive and migratory abilities.