Metabolic dysfunction-associated steatohepatitis (MASH) is the main cause of end-stage liver disease. We analyzed cell communication via ligand–receptor signaling at the single-cell level to elucidate cell-specific r...Metabolic dysfunction-associated steatohepatitis (MASH) is the main cause of end-stage liver disease. We analyzed cell communication via ligand–receptor signaling at the single-cell level to elucidate cell-specific responses and spatial zonation in MASH. We screened and validated Myd88 hyperexpression in liver sinusoidal endothelial cells and liver capsular macrophages (LCM). We showed that Myd88 levels in the periportal endothelial cells of mice with MASH were higher than those in healthy controls, correlating significantly with dysregulation of capillarization markers in vivo. Moreover, Myd88+ LCM is a primary source of diverse signaling ligands involved in inflammatory cell recruitment during diet-induced MASH. CD24-Fc bound to the inhibitory receptor SIGLECG to significantly enhance SHP1 binding to MYD88, thereby inhibiting its activation and contributing to the restoration of immune-inflammatory homeostasis in the livers of diet-induced MASH mice. CD24-Fc improved amylin liver nonalcoholic steatohepatitis-induced MASH, which was partly abolished by AAV6-mediated Myd88 knockout in vivo. These findings underscore the central role of MYD88 in MASH etiology, and the specific targeting of MYD88 in liver sinusoidal endothelial cells and LCM may be a potential therapeutic approach to slow the progression of MASH.展开更多
提出了一种用于级联结构(multi-stage noise shaping,MASH)Σ-ΔADC的自适应算法,并给出了电路实现方式.该算法采用Σ-ΔADC的输出估计输入信号幅度,在不改变噪声传输函数(noise transfer function,NTF)的前提下,通过改变调制器的缩放系...提出了一种用于级联结构(multi-stage noise shaping,MASH)Σ-ΔADC的自适应算法,并给出了电路实现方式.该算法采用Σ-ΔADC的输出估计输入信号幅度,在不改变噪声传输函数(noise transfer function,NTF)的前提下,通过改变调制器的缩放系数,得到自适应的信号传输函数(signal transfer function,STF),从而使输出信噪比(signal to noise ratio,SNR)在自适应范围内与输入信号幅度保持独立,并给出了具体的实现方法.另外,通过改变调制器最优系数适用范围的方法,将Σ-ΔADC的量化范围提高至满幅.展开更多
基金supported by Shenzhen Medical Research Fund(D2403008,China)the Medical Innovation and Development Project of Lanzhou University(lzuyxcx-2022-156,China).
文摘Metabolic dysfunction-associated steatohepatitis (MASH) is the main cause of end-stage liver disease. We analyzed cell communication via ligand–receptor signaling at the single-cell level to elucidate cell-specific responses and spatial zonation in MASH. We screened and validated Myd88 hyperexpression in liver sinusoidal endothelial cells and liver capsular macrophages (LCM). We showed that Myd88 levels in the periportal endothelial cells of mice with MASH were higher than those in healthy controls, correlating significantly with dysregulation of capillarization markers in vivo. Moreover, Myd88+ LCM is a primary source of diverse signaling ligands involved in inflammatory cell recruitment during diet-induced MASH. CD24-Fc bound to the inhibitory receptor SIGLECG to significantly enhance SHP1 binding to MYD88, thereby inhibiting its activation and contributing to the restoration of immune-inflammatory homeostasis in the livers of diet-induced MASH mice. CD24-Fc improved amylin liver nonalcoholic steatohepatitis-induced MASH, which was partly abolished by AAV6-mediated Myd88 knockout in vivo. These findings underscore the central role of MYD88 in MASH etiology, and the specific targeting of MYD88 in liver sinusoidal endothelial cells and LCM may be a potential therapeutic approach to slow the progression of MASH.
文摘针对传统的Mash结构由于各级失配导致信噪比低的问题,本文采用一阶相位累加器来实现传统的sigma-delta(Σ-Δ)架构,并将其采用硬件描述语言来实现,这样整个系统均在数字域实现,从根本上解决了各级间的失配问题.在插值滤波器的设计上,使用优化了的半带滤波器结构和级联积分梳状滤波器,节省了硬件资源.电路采用的是Magnachip 180nm 1P4M标准CMOS工艺,芯片面积只有0.2025mm^2(0.45×0.45),实测芯片得到的信噪失真比(SNDR)达到90d B.
文摘提出了一种用于级联结构(multi-stage noise shaping,MASH)Σ-ΔADC的自适应算法,并给出了电路实现方式.该算法采用Σ-ΔADC的输出估计输入信号幅度,在不改变噪声传输函数(noise transfer function,NTF)的前提下,通过改变调制器的缩放系数,得到自适应的信号传输函数(signal transfer function,STF),从而使输出信噪比(signal to noise ratio,SNR)在自适应范围内与输入信号幅度保持独立,并给出了具体的实现方法.另外,通过改变调制器最优系数适用范围的方法,将Σ-ΔADC的量化范围提高至满幅.
