ABSTRACT
AIMS: Sepsis-associated encephalopathy (SAE) is one of the most common complications of sepsis, and it might lead to long-term cognitive dysfunction and disability. This study aimed to explore the role of S100 calcium binding protein B (S100B)/RAGE/ceramide signaling pathway in SAE. MAIN METHODS: FPS-ZM1 (an inhibitor of RAGE), myriocin and GW4869 (an inhibitor of ceramide) were used to explore the role of S100B/RAGE/ceramide in acute brain injury and long-term cognitive impairment in sepsis. In addition, Mdivi-1 (inhibitor of Drp1) and Drp1 siRNA were utilized to assess the effects of C2-ceramide on neuronal mitochondria, and to explore the specific underlying mechanism in C2 ceramide-induced death of HT22 mouse hippocampal neuronal cells. KEY FINDINGS: Western blot analysis showed that sepsis significantly up-regulated S100B and RAGE. Nissl staining and Morris water maze (MWM) test revealed that inhibition of RAGE with FPS-ZM1 markedly attenuated cecal ligation and puncture (CLP)-induced brain damage and cognitive dysfunction. Furthermore, FPS-ZM1 relieved sepsis-induced C2-ceramide accumulation and abnormal mitochondrial dynamics. Moreover, inhibition of ceramide also showed similar protective effects both in vivo and in vitro. Furthermore, Mdivi-1 and Drp1 siRNA significantly reduced C2-ceramide-induced neuronal mitochondrial fragmentation and cell apoptosis in vitro. SIGNIFICANCE: This study confirmed that S100B regulates mitochondrial dynamics through RAGE/ceramide pathway, in addition to the role of this pathway in acute brain injury and long-term cognitive impairment during sepsis.
Subject(s)
Ceramides/metabolism , Receptor for Advanced Glycation End Products/metabolism , S100 Calcium Binding Protein beta Subunit/metabolism , Sepsis-Associated Encephalopathy/metabolism , Animals , Apoptosis/drug effects , Brain/metabolism , Brain Diseases/complications , Brain Diseases/metabolism , Brain Injuries/metabolism , Cognitive Dysfunction/metabolism , Disease Models, Animal , Hippocampus/metabolism , Male , Mice , Mice, Inbred C57BL , Mitochondria/drug effects , Neurons/metabolism , Sepsis/complications , Sepsis-Associated Encephalopathy/complications , Sepsis-Associated Encephalopathy/physiopathology , Signal TransductionABSTRACT
An ultracompact broadband dual-mode 3 dB power splitter using inverse design method for highly integrated on-chip mode (de) multiplexing system is proposed and experimentally demonstrated. A dual-mode convertor based on subwavelength axisymmetric three-branch waveguide is utilized to convert TE0 and TE1 to three intermediate fundamental modes. The axisymmetric topology constraint of the nanostructures enables the optimized device to achieve a strict 50:50 splitting ratio over a broad wavelength range from 1.52 to 1.60 µm. The fabricated device occupied a compact footprint of only 2.88 µm × 2.88 µm. The measured average excess losses and crosstalks for both modes were respectively less than 1.5 dB and -20 dB from 1.52 to 1.58 µm for both TE0 and TE1, which are consistent with the numerical simulations.
ABSTRACT
We propose and experimentally demonstrate a novel multimode ultra-compact mode (de)multiplexer for highly integrated on-chip mode-division multiplexing systems. This device is composed of a wide divergence angle asymmetric Y-junction based on subwavelength structure and optimized using an inverse design method. The proposed device occupied a footprint of only 2.4 × 3 µm2. The measured insertion loss and crosstalk were less than 1dB and -24 dB from 1530 nm to 1590 nm for both TE0 mode and TE1 mode, respectively. Likewise, a three mode multiplexer is also designed and fabricated with a compact footprint of 3.6 × 4.8 µm2. Furthermore, our scheme could also be expanded to include more modes.
ABSTRACT
With the development of highly densified photonic integrated circuits, the optical cross nodes number exhibits dramatically increasing. Not only efficient but also ultra-compact waveguide crossings are required to materialize the full potential of silicon photonics for on-chip optical intercross connect. In this work, we proposed several inverse-designed 4 × 4, 5 × 5 and 6 × 6 star-crossings based on the photonic-crystal-like (PhC-like) subwavelength structures, which have ultra-high port density of about 7.1 µm2/port, 5.83 µm2/port and 7.3 µm2/port respectively. Moreover, the star-crossings are practically fabricated and experimentally characterized. The average measured insertion losses (ILs) are less than 0.75, 0.9 dB and 1.5 dB, while the crosstalks are sub-22.5 dB, -20 dB and -18 dB for other output ports over 60 nm bandwidth centered at 1550 nm wavelength.
