Evoking natural thermal perceptions using a thin-film thermoelectric device with high cooling power density and speed.

Multimodal sensory feedback from upper-limb prostheses can increase their function and usability. Here we show that intuitive thermal perceptions during cold-object grasping with a prosthesis can be restored in a phantom hand through targeted nerve stimulation via a wearable thin-film thermoelectric device with high cooling power density and speed. We found that specific regions of the residual limb, when thermally stimulated, elicited thermal sensations in the phantom hand that remained stable beyond 48 weeks. We also found stimulation sites that selectively elicited sensations of temperature, touch or both, depending on whether the stimulation was thermal or mechanical. In closed-loop functional tasks involving the identification of cold objects by amputees and by non-amputee participants, and compared with traditional bulk thermoelectric devices, the wearable thin-film device reliably elicited cooling sensations that were up to 8 times faster and up to 3 times greater in intensity while using half the energy and 1/600th the mass of active thermoelectric material. Wearable thin-film thermoelectric devices may allow for the non-invasive restoration of thermal perceptions during touch.

Elevated mitochondrial activity distinguishes fibrogenic hepatic stellate cells and sensitizes for selective inhibition by mitotropic doxorubicin.

Activation of hepatic stellate cells (HSCs) is an integral component of the wound-healing process in liver injury/inflammation. However, uncontrolled activation of HSCs leads to constant secretion of collagen-rich extracellular matrix (ECM) proteins, resulting in liver fibrosis. The enhanced ECM synthesis/secretion demands an uninterrupted supply of intracellular energy; however, there is a paucity of data on the bioenergetics, particularly the mitochondrial (mito) metabolism of fibrogenic HSCs. Here, using human and rat HSCs in vitro, we show that the mito-respiration, mito-membrane potential (Δψm) and cellular 'bioenergetic signature' distinguish fibrogenic HSCs from normal, less-active HSCs. Ex vivo, HSCs from mouse and rat models of liver fibrosis further confirmed the altered 'bioenergetic signature' of fibrogenic HSCs. Importantly, the distinctive elevation in mito-Δψm sensitized fibrogenic HSCs for selective inhibition by mitotropic doxorubicin while normal, less-active HSCs and healthy human primary hepatocytes remained minimally affected if not, unaffected. Thus, the increased mito-Δψm may provide an opportunity to selectively target fibrogenic HSCs in liver fibrosis.