Previously we uncovered a critical role for norepinephrine and ␤1-adrenergic signaling in hippocampus-dependent memory retrieval. Because the ␤1 receptor couples to Gs, we examine here whether cAMP is also required for contextual memory retrieval. Using pharmacologic and genetic approaches to manipulate cAMP and downstream signaling, we demonstrate that cAMP and two of its targets, protein kinase A (PKA) and exchange protein activated by cAMP (Epac), are both required for retrieval. These findings demonstrate that cAMP signaling through Epac (as well as PKA) plays an essential role in cognition.norepinephrine ͉ protein kinase A ͉ context ͉ ␤-adrenergic ͉ cyclic AMP

Endothelial nitric oxide (NO) is a significant signaling molecule that regulates cerebral blood flow (CBF), playing a pivotal role in the prevention and treatment of cerebrovascular diseases. However, achieving the expected therapeutic efficacy is difficult using direct administration of NO donors. Therefore, endothelial nitric oxide synthase (eNOS) becomes a potential therapeutic target for cerebrovascular diseases. This review summarizes the current evidence supporting the importance of CBF to cerebrovascular function, and the roles of NO and eNOS in CBF regulation.

Along with the increasing application of nanoparticles (NPs) in many walks of life, environmental exposure to NPs has raised considerable health concerns. When NPs enter a pregnant woman’s body through inhalation, venous injection, ingestion or skin permeation, maternal toxic stress reactions such as reactive oxygen species (ROS), inflammation, apoptosis and endocrine dyscrasia are induced in different organs, particularly in the reproductive organs. Recent studies have shown that NPs disturb the developing oocyte by invading the protective barrier of theca cells, granulosa cell layers and zona pellucida. NPs disrupt sex hormone levels through the hypothalamic–pituitary-gonadal axis or by direct stimulation of secretory cells, such as granule cells, follicle cells, thecal cells and the corpus luteum. Some NPs can cross the placenta into the fetus by passive diffusion or endocytosis, which can trigger fetal inflammation, apoptosis, genotoxicity, cytotoxicity, low weight, reproductive deficiency, nervous damage, and immunodeficiency, among others. The toxicity of these NPs depend on their size, dosage, shape, charge, material and surface-coating. We summarize new findings on the toxic effect of various NPs on the ovary and on oogenesis and embryonic development. Meanwhile, we highlight the problems that need to be studied in the future. This manuscript will also provide valuable guidelines for protecting the female reproductive system from the toxicity of NPs and provide a certain reference value for NP application in the area of ovarian diseases.

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Spermatogenesis is a complicated process during which spermatogonia undergo proliferation and divisions leading, after a series of dramatic changes, to the production of mature spermatozoa. Many molecular motors are involved in this process. KIFC1, a C-terminal kinesin motor, participates in acrosome biogenesis and nuclear shaping. We report here the expression profile of KIFC1 during spermatogenesis in the Chinese mitten crab, Eriocheir sinensis. KIFC1 mainly localizes around the nucleus but is also present within the nucleus of the spermatogonium and spermatocyte. At the early spermatid stage, KIFC1 begins to be distributed on the nuclear membrane at the region where the proacrosomal vesicle is located. By the late spermatid stage, KIFC1 is found on the acrosome. Immunocytochemical and ultrastructural analyses have shown that KIFC1 localizes on the perforatorium, which is composed of an apical cap and an acrosomal tubule. We demonstrate that, during spermatogenesis in E. sinensis, KIFC1 probably plays important roles in the biogenesis of the acrosome and in its maintenance. KIFC1 may also be essential for the eversion of the acrosome during fertilization.

Background and Purpose Shenfu injection (SFI), derived from the ancient traditional Chinese medicine (Red Radix Ginseng and Radix Aconitum Carmichaeli), has been widely used in the clinical for the treatment of cardiovascular diseases for more than 20 years. The present study aims to investigate the effects of SFI and its main components on the contraction of isolated rat thoracic aorta rings and the potential mechanisms of this action.Methodology/Principal FindingsThe isolated rat thoracic aorta rings were initially treated with different concentrations of SFI, Hongshen injection (HSI, mainly containing ginsenoside) or Fupian injection (FPI, mainly containing aconite total alkaloids) separately. The control group was added an equal volume Krebs-Henseleit (K-H) solution. All three injections exhibited no obviously effects on the basal tension of the rings in the resting state. However, in the isolated thoracic aorta rings with intact endothelium, when the rings were first induced by 60 mM potassium chloride (KCl) or 1 µM norepinephrine (NE) to the maximal contraction and then treated with above injections, SFI and HSI significantly inhibited the vasoconstriction induced by KCl or NE. In addition, FPI has a tendency to inhibit KCl-induced vasoconstriction and facilitate NE-induced vasoconstriction, but no significant difference. None of them showed obvious effect on the endothelium denuded vessels. Moreover, this procedure was repeated after pre-incubation of nitric oxide synthase (NOS) inhibitor NG-nitro- L-arginine methyl ester (L-NAME), which suppressed the vasorelaxation effect of SFI and HSI.Conclusions and ImplicationsThese results demonstrate that both SFI and HSI caused an apparent thoracic aorta relaxation by endothelium-dependent manner, which was associated with eNOS system, while FPI had no detectable vasodilator effect. This suggested that the ginsenoside from red Radix Ginseng may be the main active ingredient of SFI’s vasodilator effect.

An 8-week feeding trial was conducted to evaluate the effect of replacement of fish meal (FM) with fermented soybean meal (FSM) on growth performance, intestinal morphology and microbiota of juvenile large yellow croaker (Larimichthys crocea).Replacement ratio of FM with FSM were 0%, 15%, 30%, 45%, 60% and 75%, respectively (marked as FSM0, FSM15, FSM30, FSM45, FSM60 and FSM75). The results indicated that the survival ranged from 84.78% to 99.44%, and no significant differences were observed among all treatments (p > 0.05). Weight gain ratio (WGR) and specific growth rate (SGR) significantly decreased when the replacement level of FM protein exceeded 60%, and fish fed the FSM60 and FSM75 diets had lower WGR and SGR than those fed the other diets. Feed intake (FI) and feed conversion rate (FCR) significantly increased with replacement levels of FM increasing.Illumina high-throughput sequence analyses showed that the alpha diversity did not differ among the diets of FSM0, FSM15 and FSM75. The whole community of tested samples was not modified by FSM, Firmicutes and Proteobacteria were the dominant flora in the intestines based on the phyla level. The dominant phyla in the water sample were Proteobacteria, Bacteroidetes. Fish fed the diet containing FSM75 significantly reduced the species abundance of Paenibacillus. There was a certain correlation between the intestine microbiota and SGR, antioxidant, and immune. Results indicated that up to 45% of FM can be replaced by FSM without negative effects on growth performance and intestinal integrity of juvenile large yellow croaker. K E Y W O R D Sfermented soybean meal, growth performance, intestinal morphology, Larimichthys crocea, microbiota

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