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Elabela (ELA), which is the second endogenous peptide ligand of the apelin receptor (APJ) to be discovered, has been widely studied for potential use as a therapeutic peptide. However, its role in ischemic stroke (IS), which is a leading cause of disability and death worldwide and has limited therapeutic options, is uncertain. The aim of the present study was to investigate the beneficial effects of ELA on neuron survival after ischemia and the underlying molecular mechanisms. Primary cortical neurons were isolated from the cerebral cortex of pregnant C57BL/6J mice. Flow cytometry and immunofluorescence showed that ELA inhibited oxygen–glucose deprivation (OGD) -induced apoptosis and axonal damage in vitro. Additionally, analysis of the Gene Expression Omnibus database revealed that the expression of microRNA-124-3p (miR-124-3p) was decreased in blood samples from patients with IS, while the expression of C-terminal domain small phosphatase 1 (CTDSP1) was increased. These results indicated that miR-124-3p and CTDSP1 were related to ischemic stroke, and there might be a negative regulatory relationship between them. Then, we found that ELA significantly elevated miR-124-3p expression, suppressed CTDSP1 expression, and increased p-AKT expression by binding to the APJ receptor under OGD in vitro. A dual-luciferase reporter assay confirmed that CTDSP1 was a direct target of miR-124-3p. Furthermore, adenovirus-mediated overexpression of CTDSP1 exacerbated neuronal apoptosis and axonal damage and suppressed AKT phosphorylation, while treatment with ELA or miR-124-3p mimics reversed these effects. In conclusion, these results indicated that ELA could alleviate neuronal apoptosis and axonal damage by upregulating miR-124-3p and activating the CTDSP1/AKT signaling pathway. This study, for the first time, verified the protective effect of ELA against neuronal injury after ischemia and revealed the underlying mechanisms. We demonstrated the potential for the use of ELA as a therapeutic agent in the treatment of ischemic stroke. Graphical Abstract

An efficient stereocontrolled total synthesis of (+)-biotin (1) has been achieved via the intermediacy of Roche's lactone 5 starting from cis-1,3-dibenzyl-2-imidazole-4,5-dicarboxylic acid (2). The bifunctional cinchona alkaloid-derived squaramide-promoted enantioselective alcoholysis was utilizing as a tool for the construction of two contiguous stereocenters of C-3a and C-6a in biotin molecular with excellent enantioselectivity. In addition, the 4-carboxybutyl side chain was assembled by first using C4+C1 approach via a novel tricyclic thiophanium salt intermediate.

Axle is one of the most important parts related to the safety of trailer’s operation on the railroad. In China, the checking of axles is mainly through visual inspection and hammer examinations. The construction of an automation hardware system was simulated by Pro/E, including support, guide rail, sensor, AC servomotor and servo driver conformed to the model. Next, for controlling the operation of the entire system, LabVIEW was used to write a program and to control the rotation of servomotor. The pressure heads controlled by linkage system were utilized to load the axle; meanwhile, through the PCI of NI, the data of pressure and displacement was collected. After calibration, the relative error of pinpointing sensor was 5.207%, and the average relative error was about 1.4%. Analyzed by SPSS, the voltage-load formula's correlation coefficient R is greater than 0.994, while the significance is less than 0.05, showing the regression of great significance. Finally, the capabilities of the simulated axle, such as fatigue, stiffness, intensity and stress, were analyzed carefully.

The highly enantioselective total synthesis of (+)-biotin 1 via the Hoffmann–Roche lactone–thiolactone strategy has been achieved starting from cis-1,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid 2 with an overall yield of 35%. Two contiguous stereogenic centers at C-3a and C-6a were established through a rapid cinchona alkaloid-based sulfonamide-mediated enantioselective alcoholysis of meso-cyclic anhydride 3 to afford (4S,5R)-cinnamyl hemiester 4h, the direct precursor to (3aS,6aR)-lactone 5 with high enantioselectivity. A one-pot installation of the 4-carboxybutyl side chain was accomplished by a Fukuyama coupling reaction of (3aS,6aR)-thiolactone 6 with the organozinc reagent prepared from ethyl 5-bromopentanoate.

A practical and highly regio- and stereoselective synthesis of oligoprenols starting from commercially available geraniol is described. The convergent synthetic strategy features the iterative allyl-allyl coupling of monomers easily derived from geraniol that contain one reacting terminal functional group and the repetitive reductive elimination of the p-toluenesulfonyl (Ts) groups.

A practical, highly stereoselective ten-step synthesis of coenzyme Q10 (1) has been accomplished (overall yield ca. 28%), starting from commercially available 2,3-dimethoxy-5-methylbenzoquinone (Scheme). The introduction of the first side-chain isoprenyl group with (E)-configuration (compound 6) was realized by means of a coupling reaction of the aromatic system 3 with oxirane, followed by Swern oxidation and Wittig olefination. The tosyl (Ts) group in the sulfone 9 was selectively removed with sodium naphthalenide in THF to afford 1.

A practical chemoenzymatic method for the asymmetric total synthesis of d-biotin (1) starting from the commercially available cis-1,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid (2) has been developed. The key step of the synthesis is the highly enantioselective hydrolysis of meso-dicarboxylic esters by a polymer-supported pig liver esterase and introduction of a formyl group at the C-4 position in 4 via a Grignard reaction. The polymer-supported PLE can be recovered quantitatively from the reaction mixture by simple filtration and reused without significant loss of activity.

An efficient and highly stereoselective total synthesis of d-biotin has been achieved starting from cis-1,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid (2) with an overall yield of 33%. Polymer-supported oxazaborolidine-catalyzed asymmetric reduction of meso-cyclic imide 4 constitutes the key synthetic step in introducing stereogenic centers into the d-biotin molecule.

A concise and efficient TEA-mediated desymmetrization of meso -thioanhydride 6 with 5-ethoxy-5-oxopentylzinc bromine has been developed, which affords a convenient strategy for the stereospecific total synthesis of (±)-biotin 1 .

An improved palladium(II)-catalyzed cleavage of the allyl group in allyl faropenem 2 into faropenem sodium 1 is described. The development of an efficient method for the removal of palladium impurities from the crude product 1 upon treatment with polystyrene-bound 2,4,6-trimercapto-s-triazine (polystyrene-bound TMT) led to a drastic decrease of residual palladium level from 1500−1600 ppm to less than 10 ppm in the final isolated product. The palladium(II)-catalyzed cleavage and palladium removal process demonstrated on 10 kg scale are highly convenient and efficient.

As part of a series of studies to discover new HIV reverse-transcriptase inhibitors, various novel 6alpha- and 6beta-naphthylthio 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio) thymine (HEPT) derivatives were synthesized, and in vitro anti-HIV-1 activity was evaluated. The results revealed that most of 6alpha-naphthylthio HEPT derivatives (7a-w) showed good activity [for 7e, IC50 value of 0.048 microM and selectivity index (SI) value of 735; for 7h, IC50 value of 0.057 microM and SI value of 579; for 7k, IC50 value of 0.063 microM and SI value of 565], 6beta-naphthylthio HEPT derivatives (8a-f) showed low activity, but the introduction of alpha nitro group to the C-1 position of the 6beta-naphthyl ring in the 6beta-naphthylthio series (11a-c) resulted in a dramatic increase in anti-HIV-1 activity.