The transition of single-molecule fluorescence detection and imaging from in vitro to living cells has greatly enriched our knowledge on the behavior of single biomolecules in their native environments and their roles in cellular processes. Here we review recent advances of single-molecule biophysical approaches to live-cell studies based on fluorescence imaging. We start by discussing the practical considerations in designing single-molecule fluorescence imaging in cells, including the choice of fluorescent probes, labeling methods, instrumentation, and imaging techniques. We then describe representative examples in detail to illustrate the physicochemical parameters that can be obtained by imaging individually labeled biomolecules in cells and what can be learned from such characterizations.
The role of pathological angiogenesis on liver fibrogenesis is still unknown. Here, we developed fibrotic microniches (FμNs) that recapitulate the interaction of liver sinusoid endothelial cells (LSECs) and hepatic stellate cells (HSCs). We investigated how the mechanical properties of their substrates affect the formation of capillary-like structures and how they relate to the progression of angiogenesis during liver fibrosis. Differences in cell response in the FμNs were synonymous of the early and late stages of liver fibrosis. The stiffness of the early-stage FμNs was significantly elevated due to condensation of collagen fibrils induced by angiogenesis, and led to activation of HSCs by LSECs. We utilized these FμNs to understand the response to anti-angiogenic drugs, and it was evident that these drugs were effective only for early-stage liver fibrosis in vitro and in an in vivo mouse model of liver fibrosis. Late-stage liver fibrosis was not reversed following treatment with anti-angiogenic drugs but rather with inhibitors of collagen condensation. Our work reveals stage-specific angiogenesis-induced liver fibrogenesis via a previously unrevealed mechanotransduction mechanism which may offer precise intervention strategies targeting stage-specific disease progression.
The recent EAST experimental progress since the last IAEA FEC in 2016 is presented. First demonstration of >100 seconds time scale long-pulse steady-state scenario with a good plasma performance (H98(y2) ~ 1.1) and a good control of impurity and heat exhaust with the tungsten divertor has been successfully achieved on EAST using the pure RF power heating and current drive. The extended operation regimes have been obtained (βP~2.5 & βN~1.9 of using RF&NB and βP~1.9 & βN~1.5). High bootstrap current fraction up to 47% was achieved with q95~6.0-7.0. The interaction effect between the ECH and two LHW systems has been investigated for enhanced current drive and improved confinement quality. ELM suppression using the n= 2 RMPs has been achieved at q95 (≈ 3.2-3.7) with standard type-I ELMy H-mode operational window in EAST. Reduction of the peak heat flux on the divertor was demonstrated using the active radiation feedback control. An increase in the total heating power and improvement of the plasma confinement are expected using a 0-D model prediction for higher bootstrap fraction. Towards long pulse, high bootstrap current fraction operation, a new lower ITER-like tungsten divertor with active watercooling will be installed, together with further increase and improvement of heating and current drive capability.
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