Previous imaging and postmortem studies have reported a reduction in brain volume and a decrease in the size and density of neurons in the dorsolateral prefrontal cortex (dlPFC, area 9) of subjects with major depressive disorder (MDD).1,2 These findings suggest that synapse number and function are decreased in dlPFC of depressed patients. However, there has been no direct evidence for synapse loss in MDD and the gene expression alterations underlying these effects have not been identified. Here we use microarray gene profiling and electron microscopic stereology to reveal decreased expression of synaptic function-related genes in dlPFC of MDD subjects and a corresponding reduction in the number of synapses. We also identify a transcriptional repressor that is increased in MDD, and that when expressed in PFC neurons is sufficient to decrease expression of synapse-related genes, cause loss of spines and dendrites, and produce depressive behavior in rodent models of depression.

Truncated N6-substituted-4′-oxo- and 4′-thioadenosine derivatives with C2 or C8 substitution were studied as dual acting A2A and A3 adenosine receptor (AR) ligands. The lithiation-mediated stannyl transfer and palladium-catalyzed cross coupling reactions were utilized for functionalization of the C2 position of 6-chloropurine nucleosides. An unsubstituted 6-amino group and a hydrophobic C2 substituent were required for high affinity at the hA2AAR, but hydrophobic C8 substitution abolished binding at the hA2AAR. However, most of synthesized compounds displayed medium to high binding affinity at the hA3AR, regardless of C2 or C8 substitution, and low efficacy in a functional cAMP assay. Several compounds tended to be full hA2AAR agonists. C2 substitution probed geometrically through hA2AAR-docking, was important for binding in order of hexynyl > hexenyl > hexanyl. Compound 4g was the most potent ligand acting dually as hA2AAR agonist and hA3AR antagonist, which might be useful for treatment of asthma or other inflammatory diseases.

Fluoro-homoneplanocin A (4) was synthesized from d-ribose, via the enyne ring-closing metathesis of 9, the stereoselective opening of epoxide 23a with fluoride, and a simultaneous oxidation-elimination reaction. The key intermediate 8 is expected to serve as a versatile intermediate for the synthesis of carbanucleosides.

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On the basis of the potent biological activity of cyclopentenyl-pyrimidines, fluorocyclopentenyl-pyrimidines were designed and synthesized from D-ribose. Among these, the cytosine derivative 5a showed highly potent antigrowth effects in a broad range of tumor cell lines and very potent antitumor activity in a nude mouse tumor xenograft model implanted with A549 human lung cancer cells. However, its 2'-deoxycytidine derivative 5b did not show any antigrowth effects, indicating that 2'-hydroxyl group is essential for the biological activity.

A novel AIE-based fluorescent probe for the detection of trace amounts of nitrite and nitrate ions in water has been developed, which spontaneously detects nitrites (or nitrates) by a fluorescence “turn-off” method.

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Herein, a sensitive fluorimetric assay for dissolved carbon dioxide (dCO2) was developed by using ion-induced self-assembly of a tetraphenylethylene derivative by taking advantage of its aggregation induced emission property. Chitosan, a commercially available polymer having amine functionality was utilized for the ion induced assay. In the presence of dCO2, the amine groups in the chitosan get protonated to convert neutral chitosan to a positively charged species, triggering negatively charged tetraphenylethene derivative (probe 1) to aggregate with it by electrostatic interaction. The aggregation causes intense blue fluorescence output from the system. The extent of the aggregation is reliant on the charge density of polymer, which is equivalent to dCO2 concentration. A linear relationship from 5 to 50 μM of dCO2, with a limit of detection of 5 × 10(-6) M (0.00127 hPa) was obtained. This is the first report for detecting dCO2 utilizing the AIE property.