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  • Snyder Roberson posted an update 2 weeks ago

    Dynamic Covalent Chemistry (DCC) – combining the robustness of covalent bonds with the self-correcting nature of supramolecular chemistry – facilitates the modular synthesis of complex molecular assemblies in high yields. Although numerous reactions form covalent bonds, only a small set of chemical transformations affect covalent bond formation reversibly under suitable conditions for DCC. Further progress in this area still requires the identification of dynamic motifs and greater insights into their reversibility. We have fruitfully employed DCC of both thiolate coordination to main-group elements and disulfide formation for the facile self-assembly of (1) metal/metalloid-thiolate assemblies, and (2) purely organic cyclic and caged disulfides, thioethers, and even hydrocarbons, many of which have remained elusive by traditional stepwise synthesis yet form readily through our methods. In this Minireview, we highlight the approaches to prepare these unusual compounds and the factors inducing structural transformations or favoring the formation of certain products over others, given a set of external stimuli or reaction conditions.Introduction The aim of this study was to explore whether the antibrain edema of hypertonic saline (HS) is associated with alleviating ischemic blood-brain barrier (BBB) permeability by downregulating astrocyte-derived vascular endothelial growth factor (VEGF), which is mediated by microglia-derived NOD-like receptor protein 3 (NLRP3) inflammasome. Methods The infarct volume and BBB permeability were detected. AZD2811 in vivo The protein expression level of VEGF in astrocytes in a transient focal brain ischemia model of rats was evaluated after 10% HS treatment. Changes in the NLRP3 inflammasome, IL-1β protein expression, and the interleukin-1 receptor (IL1R1)/pNF-кBp65/VEGF signaling pathway were determined in astrocytes. Results HS alleviated the BBB permeability, reduced the infarct volume, and downregulated the expression of VEGF in astrocytes. HS downregulates IL-1β expression by inhibiting the activation of the NLRP3 inflammasome in microglia and then downregulates VEGF expression by inhibiting the phosphorylation of NF-кBp65 mediated by IL-1β in astrocytes. Conclusions HS alleviated the BBB permeability, reduced the infarct volume, and downregulated the expression of VEGF in astrocytes. HS downregulated IL-1β expression via inhibiting the activation of the NLRP3 inflammasome in microglia and then downregulated VEGF expression through inhibiting the phosphorylation of NF-кBp65 mediated by IL-1β in astrocytes.Reactive oxygen species (ROS) play an important role in cellular metabolism and many oxidative stress related diseases. Oxidative stress results from toxic effects of ROS and plays a critical role in the pathogenesis of a variety of diseases like cancers and many important biological processes. It is known that the unique feature of high intracellular ROS level in cancer cells can be considered as target and utilized as a useful cancer-related stimulus to mediate intracellular drug delivery. Therefore, biomaterials responsive to excess level of ROS are of great importance in biomedical applications. In this study, a novel ROS-responsive polymer based on L-methionine poly(ester amide) (Met-PEA-PEG) was designed, synthesized, characterized and self-assembled into nano-micellar-type nanoparticles (NP). The Met-PEA-PEG NP exhibited responsiveness to an oxidative environment. The size and morphology of the nanoparticle changed rapidly in the presence of H2 O2 . The Nile Red dye was loaded into the Met-PEA-PEG NP to demonstrate a H2 O2 concentration induced time-dependent release behavior. The Met-PEA-PEG NP was sensitive to high intracellular ROS level of PC3 prostate cancer cells. Furthermore, the Met-PEA-PEG NP was investigated as a carrier of a Chinese medicine-based anticancer component, gambogic acid (GA). Compared to free GA, the GA-loaded nanocomplex (GA-NP) showed enhanced cytotoxicity toward PC3 and HeLa cells. The GA-NP also induced a higher level of apoptosis and mitochondrial depolarization in PC3 cells than free GA. The Met-PEA-PEG NP improved the therapeutic effect of GA and may serve as a potential carrier for anticancer drug delivery.Background Deeply divided ideological positions challenge collaboration when engaging youth with mental disorders, caregivers and providers in mental health research. The integrative dynamics (ID) approach can restructure relationships and overcome ‘us vs them’ thinking. Objective To assess the extent to which an experience-based co-design (EBCD) approach to patient and family engagement in mental health research aligned with ID processes. Methods A retrospective case study of EBCD data in which transitional-aged youth (n = 12), caregivers (n = 8) and providers (n = 10) co-designed prototypes to improve transitions from child to adult services. Transcripts from focus groups and a co-design event, co-designed prototypes, the resulting model, evaluation interviews and author reflections were coded deductively based on core ID concepts, while allowing for emergent themes. Analysis was based on pattern matching. Triangulation across data sources, research team, and youth and caregiver reflections enhanced rigour. Findings The EBCD focus group discussions of touchpoints in experiences aligned with ID processes of acknowledging the past, by revealing the perceived identity mythos of each group, and allowing expression of and working through emotional pain. These ID processes were briefly revisited in the co-design event, where the focus was on the remaining ID processes building cross-cutting connections and reconfiguring relationships. The staged EBCD approach may facilitate ID, by working within one’s own perspective prior to all perspectives working together in co-design. Conclusion Researchers can augment patient engagement approaches by applying ID principles with staged integration of groups to improve relations in mental health systems, and EBCD shows promise to operationalize this.Various cancer therapies have been developed, but tumor recurrence with incomplete tumor killing and remaining tumor cells/tissues is frequent in monotherapies. Herein, a nano-bio therapeutic emulsion formulated with multifunctional nanoscintillators and anaerobic Clostridium novyi-NT spores for synergistic image-guided combinational cancer therapy is reported. MRI visible nanoscintillators (NSs) are synthesized with a NaGdF4 Tb,Ce@NaGdF4 core/shell structure for an image-guided X-ray photodynamic therapy (PDT) of the normoxic peripheral tumor. An anaerobic oncolytic bacterium (C. novyi-NT) therapy is combined to treat the hypoxic central tumor tissues. Photosensitizer-coated NSs (PS-NSs) and C. novyi-NT spores are emulsified with clinically available ethiodized oil (Lipiodol) to be the nano-bio therapeutic emulsion and injected into the tumor with computed tomography image guidance. The distribution of nano-bio therapeutic emulsion, including PS-NSs and anaerobic C. novyi-NT spores in the tumor site, is confirmed by both X-ray and T1 -weighted magnetic resonance imaging.