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56 nM to 92 μM for 24 and 48 h. Effects of compounds on neurite outgrowth were evaluated by quantifying total neurite length, number of segments, and maximum neurite length per cell. Among the 84 tested compounds, neurite outgrowth in cortical neurons and motor neurons were selectively inhibited by 36 and 31 compounds, respectively. Colchicine, rotenone, and methyl mercuric (II) chloride inhibited neurite outgrowth in both cortical and motor neurons. It is interesting to note that some compounds like parathion and bisphenol AF had inhibitory effects on neurite outgrowth specifically in the cortical neurons, while other compounds, such as 2,2',4,4'-tetrabromodiphenyl ether and caffeine, inhibited neurite outgrowth in motor neurons. The data gathered from these studies show that GFP-labeled iPSC-derived human neurons are a promising tool for identifying and prioritizing compounds with developmental neurotoxicity potential for further hazard characterization.Despite recent advances in chemotherapy, pancreatic cancer remains a leading cause of cancer-related deaths. Moreover, although targeted therapy has shown promising therapeutic efficacy in many types of cancers, no such effective targeting strategy for treatment of pancreatic cancer, which is in desperate need for new treatment approaches. Here, we developed claudin-4-targeting Clostridium perfringens enterotoxin (CPE) peptide-conjugated polysialic acid nanoparticles (C-SNPs) for pancreatic cancer-targeted therapy. Doxorubicin-loaded C-SNPs (DOX-C-SNPs) higly accumulated in the targeted pancreatic cancer via enhanced peameability and retention (EPR) effect, targeting claudin-4 in pancreatic cancer that becomes superficially exposed owing to the disruption of tight junctions. Notably, DOX-C-SNP accumulation in the non-targeted, normal pancreas was significantly reduced because of hindered access to claudin-4 in tight junctions. As a result, DOX-C-SNPs substantially suppressed tumor growth in an orthotopic pancreatic cancer model while exerting minimal toxicity against non-targeted, normal tissues. Collectively, these findings indicate that claudin-4-targeting DOX-C-SNPs may have promise in treating pancreatic cancers through targeting of exposed claudin-4.Stem cell transplantation has been extensively explored to promote ischemic limb vascularization and skeletal muscle regeneration. Yet the therapeutic efficacy is low due to limited cell survival under low oxygen environment of the ischemic limbs. Therefore, continuously oxygenating the transplanted cells has potential to increase their survival. During tissue regeneration, the number of blood vessels are gradually increased, leading to the elevation of tissue oxygen content. Accordingly, less exogenous oxygen is needed for the transplanted cells. Excessive oxygen may induce reactive oxygen species (ROS) formation, causing cell apoptosis. Thus, it is attractive to develop oxygen-release biomaterials that are responsive to the environmental oxygen level. Herein, we developed oxygen-release microspheres whose oxygen release was controlled by oxygen-responsive shell. The shell hydrophilicity and degradation rate decreased as the environmental oxygen level increased, leading to slower oxygen release. The microspheres were capable of directly releasing molecular oxygen, which are safer than those oxygen-release biomaterials that release hydrogen peroxide and rely on its decomposition to form oxygen. The released oxygen significantly enhanced mesenchymal stem cell (MSC) survival without inducing ROS production under hypoxic condition. Co-delivery of MSCs and microspheres to the mouse ischemic limbs ameliorated MSC survival, proliferation and paracrine effects under ischemic conditions. It also significantly accelerated angiogenesis, blood flow restoration, and skeletal muscle regeneration without provoking tissue inflammation. The above results demonstrate that the developed microspheres have potential to augment cell survival in ischemic tissues, and promote ischemic tissue regeneration in a safer and more efficient manner.The mechanism underlying the relationship between autistic traits and social anxiety still remains unknown. It is therefore necessary to investigate potential psychological and biological mechanisms. A total of 2695 college students were samples for this research during 2017-2018. The assessed variables included demographic characteristics and measures of autistic traits, sense of security, coping styles, and social anxiety. Blood samples were collected from which DNA was extracted. https://www.selleckchem.com/products/ON-01910.html Regression analysis indicated that autistic traits and negative coping were positively associated with social anxiety; furthermore, positive coping, interpersonal security, and sense of control were negatively associated with social anxiety. Further analyses demonstrated that the relationship between autistic traits and social anxiety was mediated by coping styles (both positive coping and negative coping) and sense of security (both interpersonal security and sense of control), and coping style predicted the sense of security. The FK506 binding protein 5 (FKBP5) gene rs3800373 moderated the association between autistic traits and social anxiety. The present study is the first to demonstrate that both coping style and sense of security play an intermediate role between autistic traits and social anxiety in a sample of Chinese college students; moreover, the FKBP5 gene moderates this association between autistic traits and social anxiety. to evaluate the influence of two maternal high-fat diets with different caloric contents on anxiety-like behavior in young-adult offspring and their sensitivity to acute fluoxetine. females Wistar rats were used and divided according to diet received during gestation and lactation Control (CTR), high-fat/isocaloric (HI) and high-fat/high-caloric (HH). Offspring were subsequently divided into three subgroups according to acute administration of vehicle or fluoxetine (1 or 10 mg/kg). To assess animals' anxiety-like behaviors, three tests were used open field (OF), elevated plus-maze (EPM) and free-exploratory paradigm (FEP). In OF, HI and HH showed increased hyperactivity- and anxiety-related behaviors, HI being more hyperactive than HH. In response to fluoxetine, HI offspring decreased number of quadrants entered, decreased number of central entries and spent less time in rearing in peripheral areas, while HH offspring showed less time spent in rearing in the OF peripheral area. In EPM test, HI pups spent more time in closed arms than the HH pups.
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