Conductive hydrogels are promising interface materials utilized in bioelectronics for human-machine interactions. However, the low-temperature induced freezing problem and water evaporation-induced structural failures have significantly hindered their practical applications. To address these problems, herein, an elaborately designed nanocomposite organohydrogel is fabricated by introducing highly conductive MXene nanosheets into a tannic acid-decorated cellulose nanofibrils/polyacrylamide hybrid gel network infiltrated with glycerol (Gly)/water binary solvent. Owing to the introduction of Gly, the as-prepared organohydrogel demonstrates an outstanding flexibility and electrical conductivity under a wide temperature spectrum (from −36 to 60 °C), and exhibits long-term stability in an open environment (>7 days). Additionally, the dynamic catechol-borate ester bonds, along with the readily formed hydrogen bonds between the water and Gly molecules, further endow the organohydrogel with excellent stretchability (≈1500% strain), high tissue adhesiveness, and self-healing properties. The favorable environmental stability and broad working strain range (≈500% strain); together with high sensitivity (gauge factor of 8.21) make this organohydrogel a promising candidate for both large and subtle motion monitoring.

Excess in mitochondrial reactive oxygen species (ROS) is considered as a major cause of cellular oxidative stress. NADPH, the main intracellular reductant, has a key role in keeping glutathione in its reduced form GSH, which scavenges ROS and thus protects the cell from oxidative damage. Here, we report that SIRT5 desuccinylates and deglutarylates isocitrate dehydrogenase 2 (IDH2) and glucose-6-phosphate dehydrogenase (G6PD), respectively, and thus activates both NADPH-producing enzymes. Moreover, we show that knockdown or knockout of SIRT5 leads to high levels of cellular ROS. SIRT5 inactivation leads to the inhibition of IDH2 and G6PD, thereby decreasing NADPH production, lowering GSH, impairing the ability to scavenge ROS, and increasing cellular susceptibility to oxidative stress. Our study uncovers a SIRT5-dependent mechanism that regulates cellular NADPH homeostasis and redox potential by promoting IDH2 desuccinylation and G6PD deglutarylation.

The malate-aspartate shuttle is indispensable for the net transfer of cytosolic NADH into mitochondria to maintain a high rate of glycolysis and to support rapid tumor cell growth. The malate-aspartate shuttle is operated by two pairs of enzymes that localize to the mitochondria and cytoplasm, glutamate oxaloacetate transaminases (GOT), and malate dehydrogenases (MDH). Here, we show that mitochondrial GOT2 is acetylated and that deacetylation depends on mitochondrial SIRT3. We have identified that acetylation occurs at three lysine residues, K159, K185, and K404 (3K), and enhances the association between GOT2 and MDH2. The GOT2 acetylation at these three residues promotes the net transfer of cytosolic NADH into mitochondria and changes the mitochondrial NADH/NAD + redox state to support ATP production. Additionally, GOT2 3K acetylation stimulates NADPH production to suppress ROS and to protect cells from oxidative damage. Moreover, GOT2 3K acetylation promotes pancreatic cell proliferation and tumor growth in vivo. Finally, we show that GOT2 K159 acetylation is increased in human pancreatic tumors, which correlates with reduced SIRT3 expression. Our study uncovers a previously unknown mechanism by which GOT2 acetylation stimulates the malateaspartate NADH shuttle activity and oxidative protection.

The present study shows that topical application of ALA-PDT is a simpler, more effective and safer therapy with a lower recurrence for treatment of CA compared with conventional CO(2) laser therapy.