Anosognosia is a multifaceted syndrome characterized by a lack of awareness of motor, cognitive, or emotional deficits. While most studies have focused on basic motor disorders such as hemiplegia, only recently, the issue of whether anosognosia also concerns higher-order motor disorders like apraxia has been addressed. Here, we explore the existence of a specific form of anosognosia for apraxia in forty patients with uni-hemispheric vascular lesions. The patients were requested to imitate actions involving upper limb or bucco-facial body parts and then judge their performance. Successively, they were also asked to observe video recordings of the same actions performed by themselves or by other patients and judge the accuracy of the displayed actions. The comparison of participants versus examiner judgement and between error recognition of others' versus self's actions was considered as an index of awareness deficit for the online and offline conditions, respectively. Evidence was found that awareness deficits occurred both immediately after action execution (online anosognosia) and in the video recording task (offline anosognosia). Moreover, bucco-facial and limb apraxic patients were specifically unaware of their errors in bucco-facial and limb actions, respectively, indicating for the first time a topographical organization of the syndrome. Our approach allowed us to distinguish awareness deficits from more general disorders in error recognition; indeed, anosognosic patients were able to identify errors when the same action was executed by another patient but not when the video showed their own actions. Finally, we provide evidence that anosognosia for apraxia might be associated with frontal cortical and subcortical networks. © 2020 The British Psychological Society.Designing efficient room-temperature phosphorescence (RTP) carbon dots (C-dots) without the need of an additional matrix is important for various applications. Herein, matrix-free and highly efficient C-dots with yellow-green RTP emission have been successfully synthesized towards information encryption and decryption. Phytic acid (PA) and triethylenetetramine are used as molecular precursors, and a facile microwave-assisted heating method is selected as synthesis method. The obtained C-dots exhibit a maximum phosphorescence emission at around 535 nm under an excitation wavelength of 365 nm and a long average lifetime up to 750 ms (more than 9 s to the naked eye). PA containing six phosphate groups and serving as P source plays a significant role in producing the RTP C-dots. Furthermore, potential applications of the RTP C-dots in the field of information encryption and decryption are successfully demonstrated. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.PURPOSE Depression is a major disabling psychiatric disorder which causes severe financial burden and social consequences worldwide. Recently, (2R, 6R)-hydroxynorketamine (HNK), a metabolite of ketamine, showed strong antidepressant effect through N-methyl-D-aspartate (NMDA) antagonizing independent mechanism. In the current study the goal is to identify the potential intracellular molecules and pathways that might be involved in different therapeutic effects underlying HNK as compared to NMDA antagonist MK-801. EXPERIMENTAL DESIGN Forced-swim behavioral test, 2D fluorescence difference gel electrophoresis, and MALDI-TOF-MS/MS proteomics are used. RESULTS Compared to saline group, 14 differential proteins are identified in MK-801 treated group, with six proteins significantly up-regulated, while in HNK treated group 18 distinct proteins are identified with 11 proteins significantly up-regulated. Likewise, two proteins are significantly upregulated in HNK treated group when compared to MK-801 treated group. Among these differentially expressed proteins, phosphoglycerate mutase 1, malate dehydrogenase/ cytoplasmic, and triosephosphate isomerase are co-affected by MK-801 and HNK treatment. Representative protein expression changes are quantified by western blot, showing consistent results as determined by MALDI-TOF-MS/MS. CONCLUSION AND CLINICAL RELEVANCE The core protection mechanisms of HNK observed herein involves improving the abnormal ATP synthesis, impaired glycolysis, and the defense system therefore provides mechanistic insight and molecular targets for novel antidepressants. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The N-terminal FERM domain of focal adhesion kinase (FAK) contributes to FAK scaffolding and interacts with HER2, an oncogene and receptor tyrosine kinase. The interaction between HER2 and FAK drives resistance to FAK-kinase domain inhibitors through FAK Y397 transphosphorylation and FAK re-activation upon inhibition. As such, FAK FERM remains an attractive drug discovery target. In this report, we detail an alternative approach to targeting FAK through virtual screening-based discovery of chemical probes that target FAK FERM. We validated the binding interface between HER2 and FAK using site-directed mutagenesis and GST pull-down experiments. We assessed the ligandability of key-binding residues of HER2 and FAK utilizing computational tools. We developed a virtual screening method to screen ~200,000 compounds against the FAK FERM domain, identifying 20 virtual chemical probes. We performed GST pull-down screening on these compounds, discovering two hits, VS4 and VS14, with nanomolar IC50 s in disrupting HER2-FAK. We performed further testing, including molecular docking, immunofluorescence, phosphorylation, and cellular invasion assays to evaluate the compounds' biological effects. One probe, VS14, was identified with the ability to block both auto- and transphosphorylation of Y397. In all, these studies identify two new probes that target FAK FERM, enabling future investigation of this domain. © 2020 John Wiley & Sons A/S.One of the difficulties in the translation of gold nanoparticles (GNPs) into clinical practice is the formation of the protein corona (PC) that causes the discrepancy between the in vitro and in vivo performance of GNPs. The PC formed on the surface of GNPs gives them a biological identity instead of an initial synthetic one. In most instances, this biological identity increases the particle size, leads to more clearance by the reticuloendothelial system, and causes less uptake by target cells. However, the performance of GNPs can still be improved by rewriting their original surface chemistry via the PC. This review specifically focuses on discussing the main influence factors, including the biological environment and physicochemical properties of GNPs, which affect the production and status of the PC.  https://www.selleckchem.com/products/choline-hydroxide.html  The status of the PC such as the amount, thickness, and composition subsequently influence the biological behavior of GNPs, especially their cellular uptake, cytotoxicity, biodistribution, and tumor targeting.