The TP53 gene is a key tumor suppressor. Although the tumor suppressor p53 was one of the first to be characterized as a transcription factor, with its main function potentiated by its interaction with DNA, there are still many unresolved questions about its mechanism of action. Here, we demonstrate a novel role for p53 in the maintenance of nuclear architecture of cells. Using three-dimensional (3D) imaging and spectral karyotyping, as well as super resolution microscopy of DNA structure, we observe significant differences in 3D telomere signatures, DNA structure and DNA-poor spaces as well gains or losses of chromosomes, between normal and tumor cells with CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-deleted or wild-type TP53. Additionally, treatment with Nutlin-3 results in differences in nuclear architecture of telomeres in wild-type but not in p53 knockout MCF-7 (Michigan Cancer Foundation-7) cells. Nutlin-3 binds to the p53-binding pocket of mouse double minute 2 (MDM2) and blocks the p53-MDM2 interaction. Moreover, we demonstrate that another p53 stabilizing small molecule, RITA (reactivation of p53 and induction of tumor cell apoptosis), also induces changes in 3D DNA structure, apparently in a p53 independent manner. These results implicate p53 activity in regulating nuclear organization and, additionally, highlight the divergent effects of the p53 targeting compounds Nutlin-3 and RITA.The microstructure of ferroelectric hafnium oxide plays a vital role for its application, e.g., non-volatile memories. In this study, transmission Kikuchi diffraction and scanning transmission electron microscopy STEM techniques are used to compare the crystallographic phase and orientation of Si and Zr doped HfO2 thin films as well as integrated in a 22 nm fully-depleted silicon-on-insulator (FDSOI) ferroelectric field effect transistor (FeFET). Both HfO2 films showed a predominately orthorhombic phase in accordance with electrical measurements and X-ray diffraction XRD data. Furthermore, a stronger texture is found for the microstructure of the Si doped HfO2 (HSO) thin film, which is attributed to stress conditions inside the film stack during crystallization. For the HSO thin film fabricated in a metal-oxide-semiconductor (MOS) like structure, a different microstructure, with no apparent texture as well as a different fraction of orthorhombic phase is observed. The 22 nm FDSOI FeFET showed an orthorhombic phase for the HSO layer, as well as an out-of-plane texture of the [111]-axis, which is preferable for the application as non-volatile memory.BACKGROUND Perfectionism has been linked to suicide. According to the Narrative-Crisis Model of suicide, individuals with trait vulnerabilities are prone to develop a certain mindset, known as a Suicidal Narrative, which may precipitate the Suicide Crisis Syndrome (SCS), culminating in suicide.  https://www.selleckchem.com/products/ga-017.html  The purpose of this study was to investigate the association between perfectionism (trait vulnerability), fear of humiliation (component of the Suicidal Narrative), SCS, and prospective near-term suicidal thoughts and behaviors (STB). METHODS Adult psychiatric outpatient participants (N = 336) were assessed at baseline with the Suicidal Narrative Inventory for perfectionism and fear of humiliation. The questions used to assess perfectionism were adapted from the Multidimensional Perfectionism Scale. The severity of the SCS was calculated using the Suicide Crisis Inventory. STB were assessed at baseline and after one month using the Columbia Suicide Severity Rating Scale. Serial mediation analyses were conducted using PROCESS version 3.3 in SPSS. RESULTS While the direct effect of perfectionism on prospective STB was not significant (b = 0.01, p = 0.19), the indirect effect of perfectionism on STB, through serial mediation by fear of humiliation and the SCS, was significant (indirect effect p = 0.007, 95% CI [0.003,0.013]). The indirect effect was not significant for models that did not include both mediators. LIMITATIONS Variables were assessed at one time only. CONCLUSION Perfectionism did not directly modulate STB. Perfectionism may be related to suicidal behavior through fear of humiliation, leading to the SCS. These results support the Narrative-Crisis Model of suicide and clarify the role of perfectionism in the etiology of suicide.Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are gut hormones that are secreted from enteroendocrine L cells and K cells in response to digested nutrients, respectively. They are also referred to incretin for their ability to stimulate insulin secretion from pancreatic beta cells in a glucose-dependent manner. Furthermore, GLP-1 exerts anorexic effects via its actions in the central nervous system. Since native incretin is rapidly inactivated by dipeptidyl peptidase-4 (DPP-4), DPP-resistant GLP-1 receptor agonists (GLP-1RAs), and DPP-4 inhibitors are currently used for the treatment of type 2 diabetes as incretin-based therapy. These new-class agents have superiority to classical oral hypoglycemic agents such as sulfonylureas because of their low risks for hypoglycemia and body weight gain. In addition, a number of preclinical studies have shown the cardioprotective properties of incretin-based therapy, whose findings are further supported by several randomized clinical trials. Indeed, GLP-1RA has been significantly shown to reduce the risk of cardiovascular and renal events in patients with type 2 diabetes. However, the role of GIP in cardiovascular disease remains to be elucidated. Recently, pharmacological doses of GIP receptor agonists (GIPRAs) have been found to exert anti-obesity effects in animal models. These observations suggest that combination therapy of GLP-1R and GIPR may induce superior metabolic and anti-diabetic effects compared with each agonist individually. Clinical trials with GLP-1R/GIPR dual agonists are ongoing in diabetic patients. Therefore, in this review, we summarize the cardiovascular effects of GIP and GIPRAs in cell culture systems, animal models, and humans.Aseptic loosening and periprosthetic infections are the main causes of implant failure. Strategies to mitigate this drawback are therefore mandatory to avoid primary and revision replacement surgeries. A functional bioapatite-biopolymer double nanostructure fabricated by matrix-assisted pulsed laser evaporation to prevent infection of orthopedic and dental implants could promote osseointegration and ensure controlled delivery of natural antimicrobial drugs. The synthesized nanostructure consists of two overlapping layers, the lower from a biocompatible polymer for anticorrosive protection, and the upper of bioactive glass incorporating antimicrobial plant extract, acting as a potential drug delivery system. Morphology, composition, adherence, ability for drug delivery and biological properties (cytotoxicity and antimicrobial effect) were studied. Structures proved compact and stable, conserving a remarkable drug delivery ability for more than 21 days, i.e., enough to ensure long-term microbes' eradication.