Rapamycin directly activates lysosomal mucolipin TRP channels independent of mTOR

Rapamycin (Rap) and its derivatives, called rapalogs, are being explored in clinical trials targeting cancer and neurodegeneration. The underlying mechanisms of Rap actions, however, are not well understood. Mechanistic target of rapamycin (mTOR), a lysosomelocalized protein kinase that acts as a critical regulator of cellular growth, is believed to mediate most Rap actions. Here, we identified mucolipin 1 (transient receptor potential channel mucolipin 1 [TRPML1], also known as MCOLN1), the principle Ca2+ release channel in the lysosome, as another direct target of Rap. Patch-clamping of isolated lysosomal membranes showed that micromolar concentrations of Rap and some rapalogs activated lysosomal TRPML1 directly and specifically. Pharmacological inhibition or genetic inactivation of mTOR failed to mimic the Rap effect. In vitro binding assays revealed that Rap bound directly to purified TRPML1 proteins with a micromolar affinity. In both healthy and disease human fibroblasts, Rap and rapalogs induced autophagic flux via nuclear translocation of transcription factor EB (TFEB). However, such effects were abolished in TRPML1-deficient cells or by TRPML1 inhibitors. Hence, Rap and rapalogs promote autophagy via a TRPML1-dependent mechanism. Given the demonstrated roles of TRPML1 and TFEB in cellular clearance, we propose that lysosomal TRPML1 may contribute a significant portion to the in vivo neuroprotective and anti-aging effects of Rap via an augmentation of autophagy and lysosomal biogenesis

Nitrogen-doped porous carbon nanofibers embedded with Cu/Cu₃P heterostructures as multifunctional current collectors for stabilizing lithium anodes in lithium-sulfur batteries

Among the various beyond-lithium-ion battery systems, lithium-sulfur batteries (Li-S) have been widely considered as one of the most promising technologies owing to their high theoretical energy density. However, the irregular Li plating/stripping and infinite volume change associated with low Coulombic efficiency and safety concerns of host-less lithium anode hinder the practical application of Li-S batteries. Herein, Cu/Cu3P heterostructure-embedded in carbon nanofibers (Cu/Cu3P-N-CNFs) are developed as multifunctional current collectors for regular lithium deposition. The 3D porous interconnected carbon skeleton endows effectively reduced local current density and volume expansion, meanwhile the Cu/Cu3P particles function as nucleation sites for uniform lithium plating. Consequently, the developed ion/electron-conducting skeleton delivers remarkable electrochemical performances in terms of high Coulombic efficiency for 500 cycles at 1 mA cm−2, and the accordingly symmetric cell exhibits long-term cyclic duration over 1500 h with a low voltage hysteresis of ∼ 80 mV at 1 mA cm−2. Moreover, Li-S full cells paired with the developed anode and S@CNTs cathode also show superior rate capability (568 mAh/g at 2C) and excellent stability of &gt;500 cycles at 0.2C, further demonstrating the great potential of Cu/Cu3P-N-CNFs as promising current collectors for advanced lithium-metal batteries.</p

Spectral self-adaptive absorber/emitter for harvesting energy from the sun and outer space

The sun (~6000 K) and outer space (~3 K) are the original heat source and sink for human beings on Earth. The energy applications of absorbing solar irradiation and harvesting the coldness of outer space for energy utilization have attracted considerable interest from researchers. However, combining these two functions in a static device for continuous energy harvesting is unachievable due to the intrinsic infrared spectral conflict. In this study, we developed spectral self-adaptive absorber/emitter (SSA/E) for daytime photothermal and nighttime radiative sky cooling modes depending on the phase transition of the vanadium dioxide coated layer. A 24-hour day-night test showed that the fabricated SSA/E has continuous energy harvesting ability and improved overall energy utilization performance, thus showing remarkable potential in future energy applications.Comment: 15 pages, 4 figure