SUMMARY Most tumor cells take up more glucose than normal cells but metabolize glucose via glycolysis even in the presence of normal levels of oxygen, a phenomenon known as the Warburg effect. Tumor cells commonly express the embryonic M2 isoform of pyruvate kinase (PKM2) that may contribute to the metabolism shift from oxidative phosphorylation to aerobic glycolysis and tumorigenesis. Here we show that PKM2 is acetylated on lysine 305 and that this acetylation is stimulated by high glucose concentration. PKM2 K305 acetylation decreases PKM2 enzyme activity and promotes its lysosomal-dependent degradation via chaperone-mediated autophagy (CMA). Acetylation increases PKM2 interaction with HSC70, a chaperone for CMA, and association with lysosomes. Ectopic expression of an acetylation mimetic K305Q mutant accumulates glycolytic intermediates and promotes cell proliferation and tumor growth. These results reveal an acetylation regulation of pyruvate kinase and the link between lysine acetylation and CMA.

Flexible pressure sensors play an important role in electronic skins (E-Skins), which mimic the mechanical forces sensing properties of human skin. A rational design for a pressure sensor with adjustable characteristics is in high demand for different application scenarios. Here, we present tunable, ultrasensitive, and flexible pressure sensors based on compressible wrinkled microstructures. Modifying the morphology of polydimethylsiloxane (PDMS) microstructure enables the device to obtain different sensitivities and pressure ranges for different requirements. Furthermore, by intentionally introducing hollow structures in the PDMS wrinkles, our pressure sensor exhibits an ultrahigh sensitivity of 14.268 kPa–1. The elastic microstructure-based capacitive sensor also possesses a very low detectable pressure limit (1.5 Pa), a fast response time (<50 ms), a wide pressure range, and excellent cycling stability. Implementing respiratory monitoring and vocalization recognition is realized by attaching the flexible pressure sensor onto the chest and throat, respectively, showing its great application potential for disease diagnosis, monitoring, and other advanced clinical/biological wearable technologies.

The longtime vacancy of high-performance complementary metal-oxide-semiconductor (CMOS) technology on plastics is a non-negligible obstacle to the applications of flexible electronics with advanced functions, such as continuous health monitoring with in situ signal processing and wireless communication capabilities, in which high speed, low power consumption, and complex functionality are desired for integrated circuits (ICs). Here, we report the implementation of carbon nanotube (CNT)-based high-performance CMOS technology and its application for signal processing in an integrated sensor system for human body monitoring on ultrathin plastic foil with a thickness of 2.5 μm. The performances of both the p- and n-type CNT field-effect transistors (FETs) are excellent and symmetric on plastic foil with a low operation voltage of 2 V: width-normalized transconductances ( g/ W) as high as 4.69 μS/μm and 5.45 μS/μm, width-normalized on-state currents reaching 5.85 μA/μm and 6.05 μA/μm, and mobilities up to 80.26 cm·V·s and 97.09 cm·V·s, respectively, together with a current on/off ratio of approximately 10. The devices were mechanically robust, withstanding a curvature radius down to 124 μm. Utilizing these transistors, various high-performance CMOS digital ICs with rail-to-rail output and a ring oscillator on plastics with an oscillation frequency of 5 MHz were demonstrated. Furthermore, an ultrathin skin-mounted humidity sensor system with in situ frequency modulation signal processing capability was realized to monitor human body sweating.

The targeted degradation of membrane proteins would afford an attractive and general strategy for treating various diseases that remain difficult with the current proteolysis-targeting chimera (PROTAC) methodology. We herein report a covalent nanobody-based PROTAC strategy, termed GlueTAC, for targeted membrane protein degradation with high specificity and efficiency. We first established a mass-spectrometry-based screening platform for the rapid development of a covalent nanobody (GlueBody) that allowed proximity-enabled cross-linking with surface antigens on cancer cells. By conjugation with a cell-penetrating peptide and a lysosomal-sorting sequence, the resulting GlueTAC chimera triggered the internalization and degradation of programmed death-ligand 1 (PD-L1), which provides a new avenue to target and degrade cell-surface proteins.

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Background:The bacteria effector Tae4 is injected into the recipient cells to kill them and the immunity protein Tai4 is produced to inactivate Tae4. Results: Tae4 displays a papain-like fold, and Tai4 dimer is responsible for inhibiting Tae4 activity. Conclusion:The inactivation of Tae4 is required by collaboration of both subunits of Tai4 dimer. Significance: Our results add new insights into the effector-immunity interaction module.

Temporal and reversible control over protein and cell conjugations holds great potential for traceless release of antibody–drug conjugates (ADCs) on tumor sites as well as on-demand altering or removal of targeting elements on cell surface. We herein developed a bioorthogonal and traceless releasable reaction on proteins and intact cells to fulfill such purposes. A systematic survey of transition metals in catalyzing the bioorthogonal cleavage reactions revealed that copper complexes such as Cu­(I)-BTTAA and dual-substituted propargyl (dsPra) or propargyloxycarbonyl (dsProc) moieties offered a bioorthogonal releasable pair for reversible blockage and rescue of primary amines and phenol alcohols on small molecule drugs, protein side chains, as well as intact cell surface. For proof-of-concept, we employed such Cu­(I)-BTTAA/dsProc and Cu­(I)-BTTAA/dsPra pairs as a “traceless linker” strategy to construct cleavable ADCs to unleash cytotoxic compounds on cancer cells in situ and as a “reversible modification” strategy for cell surface engineering. Furthermore, by coupling with the genetic code expansion strategy, we site-specifically modulated ligand–receptor interactions on live cell membranes. Together, our work expanded the transition-metal-mediated bioorthogonal cleavage tool kit from terminal decaging to internal-linker breakage, which offered a temporal and reversible conjugation strategy on therapeutic proteins and cells.

A review of CNT-based high-performance flexible ICs, including the recent progresses of this technology and emerging implementation of this technology in system-level applications.