The lymphatic system:a therapeutic target for central nervous system disorders

The lymphatic vasculature forms an organized network that covers the whole body and is involved in fluid homeostasis,metabolite clearance,and immune surveillance.The recent identification of functional lymphatic vessels in the meninges of the brain and the spinal cord has provided novel insights into neurophysiology.They emerge as major pathways for fluid exchange.The abundance of immune cells in lymphatic vessels and meninges also suggests that lymphatic vessels are actively involved in neuroimmunity.The lymphatic system,through its role in the clearance of neurotoxic proteins,autoimmune cell infiltration,and the transmission of pro-inflammatory signals,participates in the pathogenesis of a variety of neurological disorders,including neurodegenerative and neuroinflammatory diseases and traumatic injury.Vascular endothelial growth factor C is the master regulator of lymphangiogenesis,a process that is critical for the maintenance of central nervous system homeostasis.In this review,we summarize current knowledge and recent advances relating to the anatomical features and immunological functions of the lymphatic system of the central nervous system and highlight its potential as a therapeutic target for neurological disorders and central nervous system repair.

Metformin promotes angiogenesis and functional recovery in aged mice after spinal cord injury by adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway

Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury.However,its effect on spinal cord injury in aged mice remains unclear.Considering the essential role of angiogenesis during the regeneration process,we hypothesized that metformin activates the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway in endothelial cells,thereby promoting microvascular regeneration in aged mice after spinal cord injury.In this study,we established young and aged mouse models of contusive spinal cord injury using a modified Allen method.We found that aging hindered the recovery of neurological function and the formation of blood vessels in the spinal cord.Treatment with metformin promoted spinal cord microvascular endothelial cell migration and blood vessel formation in vitro.Furthermore,intraperitoneal injection of metformin in an in vivo model promoted endothelial cell proliferation and increased the density of new blood vessels in the spinal cord,thereby improving neurological function.The role of metformin was reversed by compound C,an adenosine monophosphate-activated protein kinase inhibitor,both in vivo and in vitro,suggesting that the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway likely regulates metformin-mediated angiogenesis after spinal cord injury.These findings suggest that metformin promotes vascular regeneration in the injured spinal cord by activating the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway,thereby improving the neurological function of aged mice after spinal cord injury.

Numerical investigation on melting characteristics of scrap with heat and mass transfers in molten steel

Herein,a numerical simulation with simultaneous heat and mass transfers is carried out to investigate the scrap melting characteristics in molten steel after model verification by published experimental data.The numerical results show that the scrap melting stages consist of the frozen shell formation stage,the frozen shell remelting stage and the parent scrap melting stage.The heat transfer coefficient and the carbon mass transfer coefficient between the scrap and the molten steel are,respectively,in the range of 4209-6249 W m^(-2) K^(-1) and 6.4×10^(-5) m s^(-1).Meanwhile,the effects of process parameters on scrap melting time were studied.An increase in the scrap preheating temperature(T_(scrap)),the molten steel temperature(T_(steel))and the carbon content of molten steel(C_(steel)),and a decrease in the scrap thickness dscrap,can reduce the frozen shell existence time,as well as the scrap melting time.On this basis,a quantitative relationship between the aforementioned process parameters and the scrap melting time is obtained to predict the formation of frozen shell(W),which provides process guidance for shortening the scrap melting time.The quantitative relationship is expressed as:lnΨ=311.32-2.34ln(T_(scrap))-39.99ln(T_(steel))-0.08ln(d_(scrap))-0.57ln(C_(steel)).