Jing Lu,Hao Xu,Dongyue Wang,Yanlu Chen,Takeshi Inoue,Liang Gao,Kai Lei
The intricate coordination of the neural network in planarian growth and regeneration has remained largely unrevealed, partly due to the challenges of imaging the CNS in three dimensions (3D) with high resolution and within a reasonable timeframe. To address this gap in systematic imaging of the CNS in planarians, we adopted high-resolution, nanoscale imaging by combining tissue expansion and tiling light-sheet microscopy, achieving up to fourfold linear expansion. Using an automatic 3D cell segmentation pipeline, we quantitatively profiled neurons and muscle fibers at the single-cell level in over 400 wild-type planarians during homeostasis and regeneration. We validated previous observations of neuronal cell number changes and muscle fiber distribution. We found that the increase in neuron cell number tends to lag behind the rapid expansion of somatic cells during the later phase of homeostasis. By imaging the planarian with up to 120 nm resolution, we also observed distinct muscle distribution patterns at the anterior and posterior poles. Furthermore, we investigated the effects of β-catenin-1 RNAi on muscle fiber distribution at the posterior pole, consistent with changes in anterior-posterior polarity. The glial cells were observed to be close in contact with dorsal-ventral muscle fibers. Finally, we observed disruptions in neural-muscular networks in inr-1 RNAi planarians. These findings provide insights into the detailed structure and potential functions of the neural-muscular system in planarians and highlight the accessibility of our imaging tool in unraveling the biological functions underlying their diverse phenotypes and behaviors.
Jin Cui,Gongzheng Wang,Li Xian Yip,Mengzhen Dong,Mengyao Mu,Liya Tian,Yuan Gao,Qing Fan,Qiang Zhu,Xinya Zhao,Xueli Xu,David Tai Leong,Xiao Sun
Early detection and timely intervention are essential to prevent liver fibrosis from progressing to cirrhosis or hepatocellular carcinoma. Herein, utilizing the enhanced ferritin-manganese interaction by nanoplatinum growth, a novel ferritin-platinum-manganese magnetic resonance nanoplatform with RGD grafting and metformin loading (FNMMR) is developed. RGD can enhance the targeting ability of the nanoplatform toward integrin αVβ3 on activated hepatic stellate cells (aHSCs) in liver fibrosis. Systemic delivery of FNMMR shows clear degree-dependent magnetic resonance contrast enhancement in liver fibrosis. 3D reconstruction techniques and histogram-based features are achieved to qualitatively and quantitatively analyze the inhomogeneous liver fibrosis areas. FNMMR with catalase-like activity can catalyze the generation of O 2 to alleviate the liver fibrosis hypoxia and inhibit the expression of HIF-1α, blocking the TGF-β1/Smad signaling pathway. In addition, metformin shows synergy with HIF-1α reduction in blocking the TGF-β1/Smad pathway, effectively inhibiting the activation of HSCs and reducing collagen formation. Furthermore, FNMMR can achieve real-time anti-fibrotic therapy monitoring by magnetic resonance imaging. Importantly, no obvious side effects can be observed in both histological and hematology examinations. Therefore, this work presents a novel nanoplatform for accurate liver fibrosis diagnosis and synergistic anti-fibrotic therapy with real-time monitoring.
The imaging of hydrogel scaffolds by 19 F magnetic resonance imaging (MRI) represents an attractive tool for straightforward and noninvasive monitoring of their morphology and in vivo fate. However, their further applications are significantly limited by a dilemma of insufficient signal resolution with low 19 F content, and/or hydrophobic aggregation of fluorine moieties-induced signal attenuation with high 19 F content. Herein, a novel label-free fluorinated hydrogel (PFCB) is fabricated with high fluorine content to realize noninvasive monitoring through 19 F MRI under ultrahigh scanning resolution (1 mm of scanning thickness). The integration of a zwitterionic unit into each fluorine moiety completely overcame the hydrophobic aggregation-induced signal attenuation, manifesting as high 19 F content and imaging performance. Importantly, 3D reconstruction of the PFCB hydrogel in vivo can be facilely and accurately performed with background free signals, providing detailed biological information of the implanted hydrogel. Additionally, PFCB hydrogel showed adjustable and high mechanical performance, and exhibited minimum foreign body reaction after implantation. As a proof of concept, PFCB hydrogel could be further applied as gel electrodes and wireless flexible sensors for healthcare monitoring. Overall, such label-free fluorinated PFCB hydrogel is an ideal flexible scaffold for eventual clinical applications integrating 19 F MRI-guided unequivocally 3D reconstruction and healthcare monitoring.
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