Direct implantation of mesenchymal stem cells (MSCs) for cartilage and bone tissue engineering faces challenges, such as immune rejection and loss of cellular viability or functionality. As nanoscale natural particles, exosomes or small extracellular vesicles (EVs) of MSCs have potential to circumvent these problems. It is significant to investigate the impact of the tissue origin of MSCs on the therapeutic bioactivity of their corresponding EVs for cartilage and bone regeneration. Here, rat MSCs isolated from the adipose, bone marrow, and synovium are cultured to obtain their corresponding EVs (ADSC-EVs, BMSC-EVs, and SMSC-EVs, respectively). The ADSC-EVs stimulate the migration, proliferation, and chondrogenic and osteogenic differentiation of BMSCs in vitro as well as cartilage and bone regeneration in a mouse model more than the BMSC-EVs or SMSC-EVs. Proteomics analysis reveals that the tissue origin contributes to the distinct protein profiles among the three types of EVs, which induced cartilage and bone regenerative capacities by potential mechanisms of regulating signaling pathways including focal adhesion, ECM-receptor interaction, actin cytoskeleton, cAMP, and PI3K-Akt signaling pathways. Consequently, these findings provide insight that the adipose may be a superior candidate in EV-based nanomedicine for cartilage and bone regeneration. STATEMENT OF SIGNIFICANCE Extracelluar vesicles (EVs) of mesenchymal stem cells (MSCs) have been considered as a promising approach in cartilage and bone tissue engineering. In this study, for the first time, we investigated the tissue origin effect of EVs on chondrogenesis and osteogenesis of MSCs in vitro and in vivo. The results demonstrated that EVs of adipose-derived MSCs showed the most efficiency. Meanwhile, protein proteomics revealed the potential mechanisms. We provide a novel evidence that the adipose is a superior reservoir in EV-based nanotechnologies and biomaterials for cartilage and bone regeneration.With an increasing life expectancy and aging population, orthopedic defects and bone graft surgeries are increasing in global prevalence. Research to date has advanced the understanding of bone biology and defect repair mechanism, leading to a marked success in the development of synthetic bone substitutes. Yet, the quest for functionalized bone grafts prompted the researchers to find a viable alternative that regulates cellular activity and supports bone regeneration and healing process without causing serious side-effects. Recently, researchers have introduced natural medicinal compounds (NMCs) in bone scaffold that enables them to release at a desirable rate, maintains a sustained release allowing sufficient time for tissue in-growth, and guides bone regeneration process with minimized risk of tissue toxicity. According to World Health Organization (WHO), NMCs are gaining popularity in western countries for the last two decades and are being used by 80% of the population worldwide. Compared to synthetic dr an ideal scaffold should also be able to supply biological signals that actively guide tissue regeneration while simultaneously preventing post-implantation complications. Natural biomolecules are gaining popularity in tissue engineering since they possess a safer, effective approach compared to synthetic drugs. The integration of bone scaffolds and natural biomolecules exploits the advantages of customized, multi-functional bone implants to provide localized delivery of biochemical signals in a controlled manner. This review presents an overview of bone scaffolds as delivery systems for natural biomolecules, which may provide prominent advancement in bone development and improve defect-healing caused by various musculoskeletal disorders.Impaired cognitive flexibility represents a widespread symptom in psychiatric disorders, including major depressive disorder (MDD), a disease, characterized by an imbalance of neurotransmitter concentrations. While memory formation is mostly associated with glutamate, also gamma-Aminobutyric acid (GABA) and serotonin show attributions in a complex interplay between neurotransmitter systems. Treatment with selective serotonin reuptake inhibitors (SSRIs) does not solely affect the serotonergic system but shows downstream effects on GABA- and glutamatergic neurotransmission, potentially helping to restore cognitive function via neuroplastic effects. Hence, this study aims to elaborate the effects of associative relearning and SSRI treatment on GABAergic and glutamatergic function within and between five brain regions using magnetic resonance spectroscopy imaging (MRSI). In this study, healthy subjects were randomized into four groups which underwent three weeks of an associative relearning paradigm, with or withtreatment effects on GABA+/tCr ratios or effects of relearning condition on any neurotransmitter ratio could be found.  https://www.selleckchem.com/products/gsk484-hcl.html  Here, we showed a significant SSRI- and relearning-driven interaction effect of hippocampal and thalamic Glx/tCr levels, suggesting differential behavior based on different serotonin transporter and receptor densities. Moreover, an indication for Glx/tCr adaptions in the hippocampus after three weeks of SSRI treatment could be revealed. Our findings are in line with animal studies reporting glutamate adaptions in the hippocampus following chronic SSRI intake. Due to the complex interplay of serotonin and hippocampal function, involving multiple serotonin receptor subtypes on glutamatergic cells and GABAergic interneurons, the interpretation of underlying neurobiological actions remains challenging.Some psychiatric hospitals have instituted mandatory COVID-19 testing for all patients referred for admission. Others have permitted patients to decline testing. Little is known about the rate of COVID-19 infection in acute psychiatric inpatients. Characterizing the proportion of infected patients who have an asymptomatic presentation will help inform policy regarding universal mandatory versus symptom-based or opt-out testing protocols. We determined the COVID-19 infection rate and frequency of asymptomatic presentation in 683 consecutively admitted patients during the surge in the New York City region between April 3rd, 2020 and June 8th, 2020. Among these psychiatric inpatients, there was a 9.8 % overall rate of COVID-19 infection. Of the COVID-19 infected patients, approximately 76.1 % (51/67) either had no COVID-19 symptoms or could not offer reliable history of symptoms at the time of admission. Had they not been identified by testing and triaged to a COVID-19 positive unit, they could have infected others, leading to institutional outbreak.