Dopamine receptor 1 (Dop1) mediates locust attraction behaviors, however, the mechanism by which Dop1 modulates this process remains unknown to date. Here, we identify differentially expressed small RNAs associated with locust olfactory attraction after activating and inhibiting Dop1. Small RNA transcriptome analysis and qPCR validation reveal that Dop1 activation and inhibition downregulates and upregulates microRNA-9a (miR-9a) expression, respectively. miR-9a knockdown in solitarious locusts increases their attraction to gregarious volatiles, whereas miR-9a overexpression in gregarious locusts reduces olfactory attraction. Moreover, miR-9a directly targets adenylyl cyclase 2 (ac2), causing its downregulation at the mRNA and protein levels. ac2 responds to Dop1 and mediates locust olfactory attraction. Mechanistically, Dop1 inhibits miR-9a expression through inducing the dissociation of La protein from pre-miR-9a and resulting in miR-9a maturation inhibition. Our results reveal a Dop1–miR-9a–AC2 circuit that modulates locust olfactory attraction underlying aggregation. This study suggests that miRNAs act as key messengers in the GPCR signaling.

Hemodynamic overload induces pathological cardiac hypertrophy, which is an independent risk factor for intractable heart failure in long run. Beyond neurohumoral regulation, mechanotransduction has been recently recognized as a major regulator of cardiac hypertrophy under a myriad of conditions. However, the identification and molecular features of mechanotransducer on cardiomyocytes are largely sparse. For the first time, we identified Piezo1 (Piezo type mechanosensitive ion channel component 1), a novel mechanosensitive ion channel with preference to Ca 2+ was remarkably upregulated under pressure overload and enriched near T-tubule and intercalated disc of cardiomyocyte. By applying cardiac conditional Piezo1 knockout mice (Piezo1 fl/fl Myh6Cre+, Piezo1 Cko ) undergoing transverse aortic constriction, we demonstrated that Piezo1 was required for the development of cardiac hypertrophy and subsequent adverse remodeling. Activation of Piezo1 by external mechanical stretch or agonist Yoda1 lead to the enlargement of cardiomyocytes in vitro, which was blocked by Piezo1 silencing or Yoda1 analog Dooku1 or Piezo1 inhibitor GsMTx4. Mechanistically, Piezo1 perturbed calcium homeostasis, mediating extracellular Ca 2+ influx and intracellular Ca 2+ overload, thereby increased the activation of Ca 2+ -dependent signaling, calcineurin, and calpain. Inhibition of calcineurin or calpain could abolished Yoda1 induced upregulation of hypertrophy markers and the hypertrophic growth of cardiomyocytes in vitro. From a comprehensive view of the cardiac transcriptome, most of Piezo1 affected genes were highly enriched in muscle cell physiology, tight junction, and corresponding signaling. This study characterizes an undefined role of Piezo1 in pressure overload induced cardiac hypertrophy. It may partially decipher the differential role of calcium under pathophysiological condition, implying a promising therapeutic target for cardiac dysfunction.

Background Valvular heart disease (VHD) is expected to cause an increase in public-health problems in the coming years, especially in elderly populations. We aim to estimate the incidence, mortality, and burden of VHD, by age, from 1990 to 2017 in 195 countries and territories. Methods We estimated the incidence, mortality, and burden of VHD based on the Global Burden of Disease Study 2017. All metrics are presented with their 95% uncertainty intervals (UIs). The Socio-demographic Index was used to identify whether developmental status correlates with health outcomes. Results The global incidence of rheumatic heart disease (RHD) decreased by 8.67% between 1990 and 2017, while that of non-rheumatic VHD (NRVHD) increased by 45.10%. There was a 54.00% decrease in age-standardized death rate (ASDR) for RHD, but a small and non-significant decrease (-3.00%) in the ASDR for NRVHD. The global age-standardized disability-adjusted life years (DALY) rate of RHD decreased by 53.52%, while there was a 12.62% reduction in the age-standardized DALY rate of NRVHD. Conclusions The burden from different VHDs demonstrated a diverse change at a global level between 1990 and 2017. Although RHD burden has an obvious means of mitigation, a substantially high incidence of NRVHD was observed over this time period, especially in the elderly, which may lead to high health care costs and signify the potential for even higher costs in the future.

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