Saegusa Oxidation of Enol Ethers at Extremely Low Pd-Catalyst Loadings under Ligand-free and Aqueous Conditions: Insight into the Pd(II)/Cu(II)-Catalyst System.

A highly efficient and practical Pd(II)/Cu(OAc)2-catalyst system of Saegusa oxidation, which converts enol ethers to the corresponding enals with a number of diverse substrates at extremely low catalyst loadings (500 mol ppm) under ligand-free and aqueous conditions, is described. Its synthetic utility was demonstrated by large-scale applications of the catalyst system to important nature molecules. This work allows Saegusa oxidation to become a highly practical approach to preparing enals and also suggests new insight into the Pd(II)/Cu(II)-catalyst system for dehydrogenation of carbonyl compounds and decreasing Pd-catalyst loadings.

MicroRNA-135b-5p Downregulation Causes Antidepressant Effects by Regulating SIRT1 Expression.

Depression is a serious and potentially life-threatening mental illness. Recently, the role of sirtuin 1 (SIRT1) in chronic unpredictable mild stress (CUMS) management has been examined. The present study explored and clarified whether microRNA (miR)-135b-5p could play a role in depression by regulating the expression of SIRT1. SIRT1 was identified as the target gene of miR-135b-5p using TargetScan and the dual luciferase reporter assay. In addition, the expression levels of SIRT1 were significantly reduced in mouse peripheral blood and hippocampal tissue samples, while the expression of miR-135b-5p exhibited the opposite effects. Subsequently, the effects of miR-135b-5p inhibition were investigated in mice with depression. The results indicated that the miR-135b-5p inhibitor significantly increased the weight loss induced by CUMS compared with the model group, while reducing the expression levels of miR-135b-5p and further alleviating the depression-like behavior induced by CUMS. Concomitantly, the results indicated that the miR-135b-5p inhibitor inhibited CUMS-induced hippocampal cell apoptosis and significantly reduced the expression levels of cleaved caspase-3 and the ratio of cleaved caspase-3/caspase-3. Moreover, the miR-135b-5p inhibitor significantly reduced the CUMS-induced increase of the inflammatory factors IL-1ß, IL-6 and TNF-α in the hippocampal mouse samples, while significantly increasing the expression levels of SIRT1. Finally, the results demonstrated that all the effects of the miR-135b-5p inhibitor on CUMS-induced mice were significantly reversed by SIRT1 silencing. In conclusion, the present study indicated that the miR-135b-5p/SIRT1 pathway was a key mediator of antidepressant effects induced in depressed mice. Therefore, it could be considered a potential therapeutic target for the treatment of CUMS-induced depression.

Irregularity of visual motion perception and negative symptoms in schizophrenia.

Schizophrenia (SZ) is a severe psychiatric disorder characterized by perceptual, emotional, and behavioral abnormalities, with cognitive impairment being a prominent feature of the disorder. Recent studies demonstrate irregularity in SZ with increased variability on the neural level. Is there also irregularity on the psychophysics level like in visual perception? Here, we introduce a methodology to analyze the irregularity in a trial-by-trial way to compare the SZ and healthy control (HC) subjects. In addition, we use an unsupervised clustering algorithm K-means + + to identify SZ subgroups in the sample, followed by validation of the subgroups based on intraindividual visual perception variability and clinical symptomatology. The K-means + + method divided SZ patients into two subgroups by measuring durations across trials in the motion discrimination task, i.e., high, and low irregularity of SZ patients (HSZ, LSZ). We found that HSZ and LSZ subgroups are associated with more negative and positive symptoms respectively. Applying a mediation model in the HSZ subgroup, the enhanced irregularity mediates the relationship between visual perception and negative symptoms. Together, we demonstrate increased irregularity in visual perception of a HSZ subgroup, including its association with negative symptoms. This may serve as a promising marker for identifying and distinguishing SZ subgroups.

Synthesis and antimicrobial activity of polyhalobenzonitrile quinazolin-4(3H)-one derivatives.

A novel series of polyhalobenzonitrile quinazolin-4(3H)-one derivatives were synthesized and characterized by NMR, IR, MS, and HRMS spectra. All of the newly prepared compounds were screened for antimicrobial activities against four strains of bacteria (Gram-positive bacterial: Staphylococcus aureus and Bacillus cereus; Gram-negative bacterial: Escherichia coli and Pseudomonas aeruginosa) and one strain of fungi (Candida albicans). Among the synthesized compounds, 5-(dimethylamino)-8-(2,4,5-trichloro-isophthalonitrile) quinazolin-4(3H)-one (7k) exhibited significant activity towards Gram-positive bacterial, Gram-negative bacterial, and the fungi strains. The MIC (0.8-3.3µg/mL) and MBC (2.6-7.8µg/mL) for this compound were close to those of nofloxacin, chlorothalonil, and fluconazole, making it the most potent antimicrobial agents in the series.

Inactivation of GABA transaminase by 3-chloro-1-(4-hydroxyphenyl)propan-1-one.

Previously it was found that 4-hydroxybenzaldehyde is a competitive inhibitor of GABA transaminase. Here 3-chloro-1-(4-hydroxyphenyl)propan-1-one (9), a 4-hydroxybenzaldehyde analogue, was found to inactivate potently the enzyme in a time-dependent manner. alpha-Ketoglutarate prevented the enzyme from inactivation, suggesting that the inactivation occurs in its active site. Several experiments indicated that the inactivation is irreversible. This study provides a novel strategy for the design of more effective inhibitors.

[Recent progress on pharmacological effects of Gastrodia elata].

In the present review, English literature on the pharmacological effects of Gastrodia elata was summarized. The literature mainly reported the effects of G. elata on central nervous system, including anticonvulsant, neuroprotection, improvement on learning and memory, and so on. These pharmacological effects were closely associated with its phenolic components.

Inactivation of GABA transaminase by 4-acryloylphenol.

Previous study showed that 4-hydroxybenzaldehyde is a competitive inhibitor of GABA transaminase. As a result, 4-acryloylphenol was synthesized as a 4-hydroxybenzaldehyde analogue, and shown to inactivate potently the enzyme in a time-dependent manner. The inactivation was protected by alpha-ketoglutarate, indicating that it occurs at the active site of the enzyme. Beta-mercaptoethanol also prevented the enzyme from inactivation. The possible mechanism involving a Michael addition was proposed to rationalize the inactivation.

Inhibition of GABA shunt enzymes' activity by 4-hydroxybenzaldehyde derivatives.

4-Hydroxybenzaldehyde (HBA) derivatives were examined as inhibitors for GABA transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH). Investigation of structure-activity relation revealed that a carbonyl group or an amino group as well as a hydroxy group at the para position of the benzene ring are important for both enzymes' inhibition. HBA was shown to give competitive inhibition of GABA-T with respect to alpha-ketoglutarate and competitive inhibition of SSADH. 4-Hydroxybenzylamine (HBM) also showed the competitive inhibition on GABA-T with respect to GABA. In conclusion, the inhibitory effects of HBA and HBM on both enzymes could result from the similarity between both molecules and the two enzymes' substrates in structure, as well as the conjugative effect of the benzene ring. This suggested that the presence of the benzene ring may be accepted by the active site of both enzymes, HBA and HBM may be considered as lead compounds to design novel GABA-T inhibitors.