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Anti-inflammatory therapy may be an effective therapeutic intervention for neurological diseases, such as Alzheimer’s disease (AD) and stroke. As an important anti-inflammatory cytokine, interleukin-10 (IL-10) inhibits proinflammatory responses of both innate and adaptive immune cells. Panobinostat nmr We tested the hypothesis that drug-induced promotion of IL-10 expression is effective in improving cognitive abilities and neurologic outcomes of AD and stroke. An orally small molecule AD110 was synthesized and subjected to in vitro and in vivo analyses. We found that AD110 enhanced IL-10 release in lipopolysaccharide (LPS)-activated BV2 microglial cells. Y-Maze and Morris water maze tests showed improved cognitive abilities in AD mice treated with AD110. Moreover, AD110 attenuated cerebral ischemic injury in a transient middle cerebral artery occlusion (tMCAO) rat model. This study not only provides a promising lead compound with IL-10-promoting activity, but also supports the hypothesis that promoting IL-10 expression is a potential therapeutic strategy for AD and stroke.Poly(lactic acid) (PLA) as one of the most promising biodegradable polymers is being tremendously restricted in large-scale applications by the notorious toughness, ductility, and heat distortion resistance. Manufacturing PLA with excellent toughness, considerable ductility, balanced strength, and great heat distortion resistance simultaneously is still a great challenge. Natural structural materials usually possess excellent strength and toughness by elaborately constructed sophisticated hierarchical architectures, however, completely reproducing natural structural materials’ architecture have evidenced to be difficult. Inspired by the hierarchical construction of the compact bone, an innovational method with an intensive and continuous elongational flow field and facile annealing process was developed to create bone-mimicking structured PLA at an industrial scale. The bone-mimicking structured PLA with unique and novel hierarchical architectures of interlocked 3D network lamellae and large extended-chain lamellae connecting the regular lamellae was constructed by in situ formed oriented thermoplastic poly(ether)urethane nanofibers (TNFs) acting as “collagen fibers”, orderly staggered PLA lamellae behaving as “hydroxyapatite (HA) nanocrystals”, and the tenacious interface functioning as a “soft protein” adhesive layer. Attributed to the unique structure, it possesses super toughness (90.3 KJ/m2), high stiffness (2.15 GPa), balanced strength (52.6 MPa), and notable heat distortion resistance (holding at 163 °C for 1 h) simultaneously. These excellent performances of the structured PLA provide it with immense potential applications in both structural and bio-engineering materials fields such as artificial bones and tissue scaffolds.Nerve agents, the deadliest chemical warfare agents, are potent inhibitors of acetylcholinesterase (AChE) and cause rapid cholinergic crisis with serious symptoms of poisoning. Oxime reactivators of AChE are used in medical practice in the treatment of nerve agent poisoning, but the search for novel improved reactivators with central activity is an ongoing pursuit. For numerous oximes synthesized, in vitro reactivation is a standard approach in biological evaluation with little attention given to the pharmacokinetic properties of the compounds. This study reports a comprehensive physicochemical, pharmacokinetic, and safety profiling of five lipophilic 3-hydroxy-2-pyridine aldoximes, which were recently shown to be potent AChE reactivators with a potential to be centrally active. The oxime JR595 was singled out as highly metabolically stable in human liver microsomes, noncytotoxic oxime for SH-SY5Y neuroblastoma and 1321N1 astrocytoma cell lines, and its pharmacokinetic profile was determined after intramuscular administration in mice. JR595 was rapidly absorbed into blood after 15 min with simultaneous distribution to the brain at up to about 40% of its blood concentration; however, it was eliminated from both the brain and blood within an hour. In addition, the MDCKII-MDR1 cell line assay showed that oxime JR595 was not a P-glycoprotein efflux pump substrate. Finally, the preliminary antidotal study against multiple LD50 doses of VX and sarin in mice showed the potential of JR595 to provide desirable therapeutic outcomes with future improvements in its circulation time.Marine microorganisms de novo biosynthesize polyunsaturated fatty acids such as docosahexaenoic acid and eicosapentaenoic acid by polyunsaturated fatty acid (PUFA) synthases composed of three or four polypeptides in a manner similar to fatty acid synthases (FASs). FASs usually possess thioesterase (TE) domains to release free fatty acids from acyl carrier protein (ACP)-tethered intermediates. Here, we investigated the off-loading mechanism with microalgal and bacterial PUFA synthases through in vivo and in vitro experiments. The in vitro experiments with acyltransferase (AT)-like domains and acyl-ACP substrates clearly demonstrated that the AT-like domains catalyzed the hydrolysis of acyl-ACPs to yield free fatty acids.In contrast to the myriad approaches available to study protein misfolding and aggregation in vitro, relatively few tools are available for the study of these processes in the cellular context. This is in part due to the complexity of the cellular environment which, for instance, interferes with many spectroscopic approaches. Here, we describe a tripartite fusion approach that can be used to assess in vivo protein stability and solubility in the cytosol of Saccharomyces cerevisiae. Our biosensors contain tripartite fusions in which a protein of interest is inserted into antibiotic resistance markers. These fusions act to directly link the aggregation susceptibility and stability of the inserted protein to antibiotic resistance. We demonstrate a linear relationship between the thermodynamic stabilities of variants of the model folding protein immunity protein 7 (Im7) fused into the resistance markers and their antibiotic resistance readouts. We also use this system to investigate the in vivo properties of the yeast prion proteins Sup35 and Rnq1 and proteins whose aggregation is associated with some of the most prevalent neurodegenerative misfolding disorders, including peptide amyloid beta 1-42 (Aβ42), which is involved in Alzheimer’s disease, and protein α-synuclein, which is linked to Parkinson’s disease.