The transport and metabolism of lipids in cerebrovascular endothelial cells (ECs) have been hypothesized to regulate blood-brain barrier (BBB) maturation and homeostasis. Long-chain polyunsaturated fatty acids (LCPUFAs) as the important lipids components of cell membranes are essential for the development and function of BBB, but the direct links of lipid metabolism and ECs barrier function remain to be established. Here, we comprehensively characterize the transcriptomic phenotype of developmental cerebrovascular ECs in single-cell resolution and firstly find that trans-2-enoyl-CoA reductase (Tecr), a very-long-chain fatty acid synthesis, is highly expressed during barriergenesis and decreased after BBB maturation. EC-specific knockout of Tecr compromises angiogenesis due to delayed vascular sprouting. Importantly, EC-specific deletion of Tecr loss restrictive quality of vascular permeability from neonatal stages to adulthood, with high levels of transcytosis, but maintains the vascular tight junctions. Moreover, lipidomic analysis shows that the expression of Tecr in ECs is associated with the containing of omega-3 fatty acids, which directly suppresses caveolae vesicles formation. These results reveal a protective role for Tecr in BBB integrity and suggest that Tecr as a novel therapeutic target in the central nervous system (CNS) diseases associated with BBB dysfunction.
Within the hypothalamic-pituitary-gonad (HPG) axis, the major hierarchical component is gonadotropin-releasing hormone (GnRH) neurons, which directly or indirectly receive regulatory inputs from a wide array of regulatory signals and pathways, involving numerous circulating hormones, neuropeptides, and neurotransmitters, and which operate as a final output for the brain control of reproduction. In recent years, there has been an increasing interest in neuropeptides that have the potential to stimulate or inhibit GnRH in the hypothalamus of pigs. Among them, Kisspeptin is a key component in the precise regulation of GnRH neuron secretion activity. Besides, other neuropeptides, including neurokinin B (NKB), neuromedin B (NMB), neuromedin S (NMS), α-melanocyte-stimulating hormone (α-MSH), Phoenixin (PNX), show potential for having a stimulating effect on GnRH neurons. On the contrary, RFamide-related peptide-3 (RFRP-3), endogenous opioid peptides (EOP), neuropeptide Y (NPY), and Galanin (GAL) may play an inhibitory role in the regulation of porcine reproductive nerves and may directly or indirectly regulate GnRH neurons. By combining data from suitable model species and pigs, we aim to provide a comprehensive summary of our current understanding of the neuropeptides acting on GnRH neurons, with a particular focus on their central regulatory pathways and underlying molecular basis.
Reproduction in mammals is an extremely energy-intensive process and is therefore tightly controlled by the body's energy status. Changes in the nutritional status of the body cause fluctuations in the levels of peripheral metabolic hormone signals, such as leptin, insulin, and ghrelin, which provide feedback to the hypothalamus and integrate to coordinate metabolism and fertility. Therefore, to link energy and reproduction, energetic information must be centrally transmitted to Gonadotropin-releasing hormone (GnRN) neurons that act as reproductive gating. However, GnRH neurons themselves are rarely directly involved in energy information perception. Firstly, as key factors in the control of GnRH neurons, we describe the direct role of Kisspeptin and Arg-Phe amide-related peptide-3(RFRP-3) neurons in mediating metabolic signaling. Secondly, we focused on summarizing the roles of metabolic hormone-sensitive neurons in mediating peripheral energy hormone signaling. Some of these hormone-sensitive neurons can directly transmit energy information to GnRH neurons, such as Orexin neurons, etc., while others act indirectly through other neurons such as Kisspeptin and RFRP-3 neuron, such as (Pituitary adenylate cyclase-activating polypeptide)PACAP neurons, etc. In addition, as another important aspect of the integration of metabolism and reproduction, the impact of reproductive signaling itself on metabolic function were also considered, as exemplified by our examination of the role of Kisspeptin and RFRP-3 in feeding control. This review summarizes the latest research progress in related fields, in order to more fully understand the central neuropeptide network that integrates energy metabolism and reproduction.
Wind-induced vibration coefficient β is an essential parameter for the structural wind-resistant design. In order to provide accurate design wind loads, β of a landscape tower with curved and twisted columns and spiral beams (short for LT) is studied by wind tunnel test and numerical simulation. The results show that the displacement wind-induced vibration coefficient is greatly affected by wind yaw angle. Moreover, the inertial load wind-induced vibration coefficients increase along the height and increase sharply at the platform position. Due to the influence of nonuniform shape and mass distribution and wind yaw angle, β calculated by the Chinese and American load code does not apply to LT structures. In addition, this article puts forward some suggestions for the shortcoming in the use of code to calculate β of LTs and made some prospects for future research on wind-resistant design of LTs, hoping to provide theoretical guidance and thinking inspiration for future research.
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