Manikandan Ramasamy, Gen Li, Lei Guo, Hong Fang, Ayman Eid, Rushil Mandlik, Yanhao Cheng, Randall P Niedz, James N Culver, Gary D Coleman, Zhongchi Liu, Kranthi K Mandadi, Yiping Qi
Quantitative analysis showed that ZLE is rich in polysaccharides, terpenes, and flavonoids. UPLC-MS/MS identified 389 phytochemical constituents, predominantly iridoid glycosides, organic acids, and flavonoids. In adenosine-induced HepG2 cells, ZLE significantly reduced UA production and xanthine oxidase (XOD) activity. In HUA mice, ZLE dose-dependently decreased serum UA levels, improved renal and hepatic function by reducing serum creatinine, blood urea nitrogen, alanine aminotransferase, and aspartate aminotransferase levels, and inhibited hepatic XOD activity. Furthermore, ZLE restored renal urate homeostasis through coordinated regulation of key urate transporters and alleviated HUA-induced renal inflammation and histopathological injury by suppressing the lipopolysaccharide-mediated NLRP3/Caspase-1 signaling pathway.
A major bottleneck in genome editing of many perennial plants is their recalcitrance to transformation and regeneration. To boost genome editing in such perennial crops, transcriptional reprogramming of morphogenic genes is introduced by CRISPR-Combo, a versatile system for simultaneous genome editing and transcriptional activation in plant cells. In potato, we screen 17 morphogenic genes and identify 4 genes (WOX11/12, ARF5, ABI3-1, and ABI3-2) that promote regeneration of genome-edited hairy roots, and 3 of the 4 genes are also found to boost shoot regeneration by Agrobacterium-mediated stable transformation. Similarly, screening of 10 morphogenic genes in citrus leads to the identification of 5 genes (BBM3, FUS3, IPT1, SERK1, and STM) that enhance plant regeneration upon activation. In wild strawberry, we demonstrate that simultaneous activation of Baby Boom genes (BBM1 and BBM2) or of GRF3 and GIF1 reduces the generation time of genome-edited plants by over one month. Moreover, in poplar, we show that simultaneous activation of WUS and WOX11 synergistically promotes plant regeneration without exogenous plant hormones, which leads to a protocol of generating genome-edited poplar shoots in less than one month. Collectively, this study provides efficient strategies for boosting genome editing in four perennial crops.