Fenton/Fenton-like metal-based nanomaterials combine with oxidase for synergistic tumor therapy

Chemodynamic therapy (CDT) catalyzed by transition metal and starvation therapy catalyzed by intracellular metabolite oxidases are both classic tumor treatments based on nanocatalysts. CDT monotherapy has limitations including low catalytic efficiency of metal ions and insufficient endogenous hydrogen peroxide (H2O2). Also, single starvation therapy shows limited ability on resisting tumors. The “metal-oxidase” cascade catalytic system is to introduce intracellular metabolite oxidases into the metal-based nanoplatform, which perfectly solves the shortcomings of the above-mentioned monotherapiesIn this system, oxidases can not only consume tumor nutrients to produce a “starvation effect”, but also provide CDT with sufficient H2O2 and a suitable acidic environment, which further promote synergy between CDT and starvation therapy, leading to enhanced antitumor effects. More importantly, the “metal-oxidase” system can be combined with other antitumor therapies (such as photothermal therapy, hypoxia-activated drug therapy, chemotherapy, and immunotherapy) to maximize their antitumor effects. In addition, both metal-based nanoparticles and oxidases can activate tumor immunity through multiple pathways, so the combination of the “metal-oxidase” system with immunotherapy has a powerful synergistic effect. This article firstly introduced the metals which induce CDT and the oxidases which induce starvation therapy and then described the “metal-oxidase” cascade catalytic system in detail. Moreover, we highlight the application of the “metal-oxidase” system in combination with numerous antitumor therapies, especially in combination with immunotherapy, expecting to provide new ideas for tumor treatment.

Effect of Lubricant Starvation on the Tribo-Dynamic Behavior of Linear Roller Guideway

This paper presents an experimentally validated numerical approach linear roller guideways considering coupled vertical and horizontal (feed) motions and taking into account lubricant starvation. The inlet starvation is considered by incorporating potential flow method. Results show that starvation has pronounced effect on the lubricant film thickness, friction, and applied load on contact by up to 32%. Localised pressure values may vary by up to 100%. The severity of starvation effect is frequency dependent. It is also revealed that the starvation effect can be controlled by the amount of preload on linear guideway.

A biomimetic MOF nanoreactor enables synergistic suppression of intracellular defense systems for augmented tumor ablation

A homotypic cancer cell membrane camouflaged MOF-based nanoreactor with the photothermal–starvation effect has been developed for synergistic suppression of intracellular defensive systems for enhanced cancer treatment.

Up-regulation of lysosomal TRPML1 channels is essential for lysosomal adaptation to nutrient starvation

Upon nutrient starvation, autophagy digests unwanted cellular components to generate catabolites that are required for housekeeping biosynthesis processes. A complete execution of autophagy demands an enhancement in lysosome function and biogenesis to match the increase in autophagosome formation. Here, we report that mucolipin-1 (also known as TRPML1 or ML1), a Ca2+ channel in the lysosome that regulates many aspects of lysosomal trafficking, plays a central role in this quality-control process. By using Ca2+ imaging and whole-lysosome patch clamping, lysosomal Ca2+ release and ML1 currents were detected within hours of nutrient starvation and were potently up-regulated. In contrast, lysosomal Na+-selective currents were not up-regulated. Inhibition of mammalian target of rapamycin (mTOR) or activation of transcription factor EB (TFEB) mimicked a starvation effect in fed cells. The starvation effect also included an increase in lysosomal proteostasis and enhanced clearance of lysosomal storage, including cholesterol accumulation in Niemann–Pick disease type C (NPC) cells. However, this effect was not observed when ML1 was pharmacologically inhibited or genetically deleted. Furthermore, overexpression of ML1 mimicked the starvation effect. Hence, lysosomal adaptation to environmental cues such as nutrient levels requires mTOR/TFEB-dependent, lysosome-to-nucleus regulation of lysosomal ML1 channels and Ca2+ signaling.

A role for AMPK in increased insulin action after serum starvation

Serum starvation is a common cell culture procedure for increasing cellular response to insulin, though the mechanism for the serum starvation effect is not understood. We hypothesized that factors known to potentiate insulin action [e.g., AMP-activated protein kinase (AMPK) and p38] or to be involved in insulin signaling leading to glucose transport [e.g., Akt, PKCζ, AS160, and ataxia telangiectasia mutated (ATM)] would be phosphorylated during serum starvation and would be responsible for increased insulin action after serum starvation. L6 myotubes were incubated in serum-containing or serum-free medium for 3 h. Levels of phosphorylated AMPK, Akt, and ATM were greater in serum-starved cells than in control cells. Serum starvation did not affect p38, PKCζ, or AS160 phosphorylation or insulin-stimulated Akt or AS160 phosphorylation. Insulin had no effect on glucose transport in control cells but caused an increase in glucose uptake for serum-starved cells that was preventable by compound C (an AMPK inhibitor), by expression of dominant negative AMPK (AMPK-DN), and by KU55933 (an ATM inhibitor). ATM protein levels increased during serum starvation, and this increase in ATM was prevented by compound C and AMPK-DN. Thus, it appears that AMPK is required for the serum starvation-related increase in insulin-stimulated glucose transport, with ATM as a possible downstream effector.

SIZE EFFECT ON DEFORMATION MODE IN MICRON-SIZED Ti-5Al SINGLE CRYSTAL LOADED ALONG $[2\,\overline 1 \,\overline 1 \,0]$ AND [0001]

Free-standing sub-micron Ti -5 Al single crystal square pillars were fabricated along [Formula: see text] double slip and [0001] twinning orientations using FIB fabrication processes. Samples in range of 0.4 to 2.0µm were compressed. The yield stress increases much higher than their bulk counterpart as the specimen width decreases. The tendency of "smaller is stronger" is displayed in Ti -5 Al single crystals loaded along [Formula: see text] and [0001] orientations. The number of slip systems is restricted by specimen physical size as it declines from 2µm to 0.5µm, when the specimens were subjected to double slip loading. Meanwhile, when sample size is less than 1.0µm, micro-pillars along twinning orientation have to compensate the incomplete twinning deformation via shearing due to geometrical restriction and dislocation starvation effects. This variation of deformation mode could be attributed to the starvation effect of dislocations.