The nuclear receptor retinoic acid receptor-related orphan receptor gamma (RORγ or RORc) is a key transcription factor for the production of pro-inflammatory cytokines implicated in the pathogenesis of autoimmune diseases. Recently, small molecule inhibitors of RORc drew the enormous attention of the research community worldwide as a possible therapy for autoimmune diseases, mediated by the IL-17 cytokine. With the clinical proof-of-concept inferred from a small molecule inhibitor VTP-43742 for psoriasis and recent inflow of several RORc inhibitors into the clinic for therapeutic interventions in autoimmune diseases, this field continues to evolve. This review briefly summarizes the RORc inhibitors disclosed in the literature and discusses the progress made by these inhibitors in combating autoimmune diseases.
An exact nonlinear Alfvén wave in a low-β plasma is investigated. Super Alfvén solitons with a density depression are found to exist. The analytical result for the small-amplitude soliton is given.
It is well-known that an extraordinary wave propagating along the density gradient mode converts into an electron Bernstein wave at the upper-hybrid layer. This paper reports various kinds of nonlinear effects associated with the electrostatic waves. Specifically, numerous possibilities of the three-wave decay interaction and the process of modulational instabilities are considered. The growth rate and threshold are obtained analytically. A comparative study of the growth rates and thresholds is carried out so as to emphasize the importance of slow plasma response. Also investigated were the effects of the pump profile, and the plasma nonuniformities on the temporal increment. Application of this work to tokamak devices, laboratory plasmas, as well as space plasmas, is discussed.
This paper presents a scheme to achieve THz radiation by the beating of cosh-Gaussian lasers in spatially periodic density plasma (ripple density). Here, the lasers exert a nonlinear ponderomotive force along the transverse direction which imparts an oscillatory velocity to electrons that couples with the density ripple to generate a stronger transient transverse current due to the spatial variation of their fields, driving THz radiation. The importance of laser-beam-width parameters, decentred parameter, amplitude and periodicity of the density structure are discussed for THz emission. By changing the decentred parameter the peak intensity of lasers can be shifted in the transverse direction and a notable change is found in the magnitude of THz field amplitude and its conversion efficiency.
NLRP3 inflammasome mediated release of interleukin-1β (IL-1β) has been implicated in various diseases. In this study, rationally designed mimics of sulfonylurea moiety were investigated as NLRP3 inhibitors. Our results culminated into discovery of series of unprecedented N-cyano sulfoximineurea derivatives as potent NLRP3 inflammasome inhibitors. Compound 15 (IC 50 = 7 nM) and analogues were found to be highly potent and selective NLRP3 inflammasome inhibitor with good pharmacokinetic profile. These effects translate in vivo, as 15, 29, and 34 significantly inhibit NLRP3 dependent IL-1β secretion in mice.
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