The vitellogenin receptor functionality of the migratory locust depends on its phosphorylation by juvenile hormone.

Vitellogenin receptor (VgR) plays a pivotal role in ovarian vitellogenin (Vg) uptake and vertical transmission of pathogenic microbes and Wolbachia symbionts. However, the regulatory mechanisms of VgR action as an endocytic receptor and translocation from oocyte cytoplasm to the membrane remain poorly understood. Here, by using the migratory locust Locusta migratoria as a model system, we report that juvenile hormone (JH) promotes VgR phosphorylation at Ser1361 in the second EGF-precursor homology domain. A signaling cascade including GPCR, PLC, extracellular calcium, and PKC-ι is involved in JH-stimulated VgR phosphorylation. This posttranslational regulation is a prerequisite for VgR binding to Vg on the external surface of the oocyte membrane and subsequent VgR/Vg endocytosis. Acidification, a condition in endosomes, induces VgR dephosphorylation along with the dissociation of Vg from VgR. Phosphorylation modification is also required for VgR recycling from oocyte cytoplasm to the membrane. Additionally, VgR phosphorylation and its requirement for Vg uptake and VgR recycling are evolutionarily conserved in other representative insects including the cockroach Periplaneta americana and the cotton bollworm Helicoverpa armigera This study fills an important knowledge gap of low-density lipoprotein receptors in posttranslational regulation, endocytosis, and intracellular recycling.

Efficacy of urapidil for the treatment of patients with senile hypertension and acute heart failure.

BACKGROUND: Previous clinical studies have reported that urapidil can effectively treat patients with senile hypertension (SH) and acute heart failure (AHF). However, no studies have systematically assessed the efficacy and safety of urapidil for patients with SH and AHF. Thus, this study will investigate the efficacy and safety of urapidil for SH and AHF. METHODS: In this study, we will search the following electronic databases from inception to the June 30, 2019: MEDLINE, EMBASE, Cochrane Library, Google scholar, Springer, WANGFANG, and China Knowledge Resource Integrated Database. We will search all these electronic databases without language limitations. We will also search grey records to avoid missing potential literature. In this study, only randomized controlled trials on assessing efficacy and safety of urapidil for SH and AHF will be considered. We will use RevMan 5.3 software and STATA 15.0 software to carry out statistical analysis. RESULTS: This study will evaluate the efficacy and safety of urapidil for SH and AHF by assessing all-cause mortality, change in body weight, urine output, change in serum sodium; and incidence of all adverse events. CONCLUSION: This study will provide latest evidence of the efficacy and safety of urapidil for patients with SH and AHF. DISSEMINATION AND ETHICS: This study will only analyze published data; therefore, no ethical approval is needed. The findings of this study will be published at peer-reviewed journals. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019139344.

Efficacy of methylprednisolone for treatment of persistent vertigo.

BACKGROUND: This study will systematically investigate the efficacy and safety of methylprednisolone for treatment of persistent vertigo (PV). METHODS: All following electronic databases will be searched from inception to the June 30, 2019 without language restrictions: MEDILINE, EMBASE, Cochrane Library, Web of Science, and Chinese Biomedical Literature Database. All randomized controlled trials focusing on assessing the efficacy and safety of methylprednisolone for patients with PV will be fully considered for inclusion. Cochrane risk of bias tool will be used for assessing methodological quality, and RevMan 5.3 software (Cochrane Community, London, UK) will be utilized for statistical analysis. RESULTS: This study will assess the efficacy and safety of methylprednisolone for PV via assessing primary outcome of vertigo, and secondary outcomes of somatization, depression, anxiety, health-related quality of life, and adverse events. CONCLUSION: This study will provide a high-quality evidence to judge whether methylprednisolone is an effective and safety therapy for patients with PV. DISSEMINATION AND ETHICS: No individual data will be utilized in this study, thus, it does not need ethical approval. The results of this study will be published at peer-reviewed journals. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019138890.

Protein kinase C mediates juvenile hormone-dependent phosphorylation of Na+/K+-ATPase to induce ovarian follicular patency for yolk protein uptake.

In oviparous animals, vitellogenesis is prerequisite to egg production and embryonic growth after oviposition. For successful insect vitellogenesis and oogenesis, vitellogenin (Vg) synthesized in the fat body (homologue to vertebrate liver and adipose tissue) must pass through the intercellular channels, a condition known as patency in the follicular epithelium, to reach the surface of oocytes. This process is controlled by juvenile hormone (JH) in many insect species, but the underlying mechanisms remain elusive. Previous work has suggested the possible involvement of Na+/K+-ATPase in patency initiation, but again, the regulatory cascade of Na+/K+-ATPase for patency initiation has been lacking. Using the migratory locust Locusta migratoria as a model system, we report here that RNAi-mediated knockdown of gene coding for Na+/K+-ATPase, inhibition of its phosphorylation, or suppression of its activity causes loss of patency, resulting in blocked Vg uptake, arrested oocyte maturation, and impaired ovarian growth. JH triggers G protein-coupled receptor (GPCR), receptor tyrosine kinase (RTK), phospholipase C (PLC), inositol trisphosphate receptor (IP3R), and protein kinase C (PKC) to phosphorylate Na+/K+-ATPase α-subunit at amino acid residue Ser8, consequently activating Na+/K+-ATPase for the induction of patency in vitellogenic follicular epithelium. Our results thus point to a previously unidentified mechanism by which JH induces the phosphorylation and activation of Na+/K+-ATPase via a signaling cascade of GPCR, RTK, PLC, IP3R, and PKC. The findings advance our understanding of JH regulation in insect vitellogenesis and oogenesis.