2-(4-Chloro­phen­yl)-5-(3,4-dimethoxy­pheneth­yl)-6,7-dihydro­pyrazolo[1,5-a]pyrazin-4(5H)-one

In the title compound, C22H22ClN3O3, the dihedral angles between the planes of the benzene rings and the pyrazole ring are 16.05 (10) and 84.84 (10)°. The conformation of the six-membered heterocyclic ring is close to a screw-boat. The crystal packing is stabilized by weak inter­molecular C—H⋯O inter­actions and is also consolidated by C—H⋯π inter­actions

Current Reversals in a inhomogeneous system with asymmetric unbiased fluctuations

We present a study of transport of a Brownian particle moving in periodic symmetric potential in the presence of asymmetric unbiased fluctuations. The particle is considered to move in a medium with periodic space dependent friction. By tuning the parameters of the system, the direction of current exhibit reversals, both as a function of temperature as well as the amplitude of rocking force. We found that the mutual interplay between the opposite driving factors is the necessary term for current reversals.Comment: 9 pages, 7 figure

FSD-C10, a Fasudil derivative, promotes neuroregeneration through indirect and direct mechanisms.

FSD-C10, a Fasudil derivative, was shown to reduce severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through the modulation of the immune response and induction of neuroprotective molecules in the central nervous system (CNS). However, whether FSD-C10 can promote neuroregeneration remains unknown. In this study, we further analyzed the effect of FSD-C10 on neuroprotection and remyelination. FSD-C10-treated mice showed a longer, thicker and more intense MAP2 and synaptophysin positive signal in the CNS, with significantly fewer CD4(+) T cells, macrophages and microglia. Importantly, the CNS of FSD-C10-treated mice showed a shift of activated macrophages/microglia from the type 1 to type 2 status, elevated numbers of oligodendrocyte precursor cells (OPCs) and oligodendrocytes, and increased levels of neurotrophic factors NT-3, GDNF and BDNF. FSD-C10-treated microglia significantly inhibited Th1/Th17 cell differentiation and increased the number of IL-10(+) CD4(+) T cells, and the conditioned medium from FSD-C10-treated microglia promoted OPC survival and oligodendrocyte maturation. Addition of FSD-C10 directly promoted remyelination in a chemical-induced demyelination model on organotypic slice culture, in a BDNF-dependent manner. Together, these findings demonstrate that FSD-C10 promotes neural repair through mechanisms that involved both immunomodulation and induction of neurotrophic factors

Geraniol attenuates virulence factors by inhibiting quorum sensing of Pseudomonas aeruginosa

Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen that can cause severe respiratory tract infections. Geraniol, a chemical component of essential oils, has antimicrobial and anti-inflammatory activities, along with low toxicity. However, the effect and mechanism of geraniol against P. aeruginosa virulence factors are rarely studied. In this study, we investigated the quorum sensing (QS) inhibitory effects and mechanisms of geraniol against P. aeruginosa PAO1, using physiological and biochemical techniques, quantitative reverse transcription polymerase chain reaction, and transcriptomics. Geraniol slightly affected P. aeruginosa PAO1 growth, prolonged the lag phase, and delayed growth periods in a concentration-dependent manner. Geraniol inhibited three QS systems of P. aeruginosa, las, rhl, and pqs by suppressing the expression level of their key genes, including the three signal synthetase encoding genes of lasI, rhlI, and pqsABCDEH, and the corresponding signal receptor encoding genes of lasR, rhlR, and pqsR. Geraniol also suppressed certain virulence genes regulated by these three QS systems, including rhlABC, lasAB, lecAB, phzABMS, and pelABG, resulting in the attenuation of the related virulence factors, rhamnolipids, exoprotease LasA, elastase, lectin, pyocyanin, and biofilm. In conclusion, geraniol can suppress the virulence factors of P. aeruginosa PAO1 by inhibiting the three QS systems of las, rhl, and pqs. This study is significant for improving the treatment of bacterial infections caused by P. aeruginosa