ABSTRACT
Objective@#To explore the effect of ambient fine particulate matters (PM2.5) and temperature interaction on schizophrenia admission.@*Methods@#All admission data were retrieved from the Psychiatric Hospital and Municipal Hospital of TongLing from January 1, 2014 to December 31, 2017. Daily air pollution and meteorological data were collected from the Tongling Environmental Protection Agency and Meteorological Bureau, respectively. A distributed lag non-linear model combined with the generalized additive model were applied to explore the effects of PM2.5, multi-pollutants, and the interaction between temperature and PM2.5 on schizophrenia admission. The stratification of temperature was divided by three criteria. The low temperature layer was defined as <P5 or <P10 or <P20; P5-P95 or P10-P90 or P20-P80 was defined as the middle temperature layer; >P95 or >P90 or >P80 was defined as the high temperature layer.@*Results@#From 2014 to 2017, 6 642 patients were admitted for schizophrenia in Tongling, and the median of PM2.5 and temperature were 47.0 μg/m3 and 17.5 ℃, respectively. The median concentration of PM2.5 (P50) was taken as a reference. When the exposure concentration of PM2.5 was P90, the lagged effect appeared in the first day with RR=1.03 (95%CI: 1.00-1.07) and reached the maximum in the fifth day with RR=1.16 (95%CI: 1.13-1.19). In the multi-pollutant models, it was found that the simultaneous inclusion of PM2.5 and NO2 had higher risk of schizophrenia admission, with the RR=1.18 (95%CI: 1.15-1.22), P<0.001. The risk of schizophrenia admission caused by PM2.5 exposure at high temperature was greatest under the three temperature stratification standards, which were 12.1% (8.5%-15.7%), 9.7% (6.9%-12.6%) and 17.1% (11.6%-22.8%), all P values <0.001.@*Conclusion@#With the increase of PM2.5 concentration, the risk of schizophrenia admission is increased, and the risk effect of PM2.5 is stronger at high temperature.
ABSTRACT
The Hippo pathway plays key roles in animal development. It suppresses tumorigenesis by controlling the transcription of the target genes that are critical for cell proliferation and apoptosis. The transcriptional coactivator YAP is the major downstream effector of the Hippo signaling. Upon extracellular stimulation, a kinase cascade in the Hippo pathway phosphorylates YAP and promotes its cytoplasmic sequestration by 14-3-3 and ubiquitin-dependent degradation. When the Hippo pathway is turned off, YAP (which lacks a DNA-binding domain) is dephosphorylated and translocates to the nucleus, where it associates with the transcription factor TEAD to form a functional heterodimeric transcription factor and to promote the expression of the Hippo-responsive genes. Recently, structures of the YAP-binding domain of TEAD alone or in complex with YAP have revealed the atomic details of the TEAD-YAP interaction. Here, I review these exciting advances, propose a strategy for targeting the TEAD-YAP interaction using small molecules, and suggest potential mechanisms by which phosphorylation and 14-3-3 binding regulate the cytoplasmic retention of YAP.