HTR2A agonists play a therapeutic role by restricting ILC2 activation in papain-induced lung inflammation

Group 2 innate lymphoid cells(ILC2s)are a category of heterogeneous cells that produce the cytokines IL-5 and IL-13,which mediate the type 2 immune response.However,specific drug targets on lung ILC2s have rarely been reported.Previous studies have shown that type 2 cytokines,such as IL-5 and IL-13,are related to depression.Here,we demonstrated the negative correlation between the depression-associated monoamine neurotransmitter serotonin and secretion of the cytokines IL-5 and IL-13 by ILC2s in individuals with depression.Interestingly,serotonin ameliorates papain-induced lung inflammation by suppressing ILC2 activation.Our data showed that the serotonin receptor HTR2A was highly expressed on ILC2s from mouse lungs and human PBMCs.Furthermore,an HTR2A selective agonist(DOI)impaired ILC2 activation and alleviated the type 2 immune response in vivo and in vitro.Mice with ILC2-specific depletion of HTR2A(Il5^(cre/+)·Htr2a^(flox/flox)mice)abolished the DOI-mediated inhibition of ILC2s in a papain-induced mouse model of inflammation.In conclusion,serotonin and DOI could restrict the type 2 lung immune response,indicating a potential treatment strategy for type 2 lung inflammation by targeting HTR2A on ST2+ILC2s.

Seismic attenuation compensation with spectral-shaping regularization

Because of the viscoelasticity of the subsurface medium,seismic waves will inherently attenuate during propagation,which lowers the resolution of the acquired seismic records.Inverse-Q filtering,as a typical approach to compensating for seismic attenuation,can efficiently recover high-resolution seismic data from attenuation.Whereas most efforts are focused on compensating for highfrequency energy and improving the stability of amplitude compensation by inverse-Q filtering,low-frequency leakage may occur as the high-frequency component is boosted.In this article,we propose a compensation scheme that promotes the preservation of lowfrequency energy in the seismic data.We constructed an adaptive shaping operator based on spectral-shaping regularization by tailoring the frequency spectra of the seismic data.We then performed inverse-Q filtering in an inversion scheme.This data-driven shaping operator can regularize and balance the spectral-energy distribution for the compensated records and can maintain the low-frequency ratio by constraining the overcompensation for high-frequency energy.Synthetic tests and applications on prestack common-reflectionpoint gathers indicated that the proposed method can preserve the relative energy of low-frequency components while fulfilling stable high-frequency compensation.