De novo and acquired resistance, largely attributed to genetic alterations, are barriers to effective anti-EGFR therapy. We generated cetuximab-resistant cells following prolonged cetuximab exposure to cetuximab-sensitive colorectal cancer cells in three-dimensional culture. Through whole exome sequencing and transcriptional profiling, we found overexpression of lncRNA MIR100HG and two embedded miRNAs, miR-100 and miR-125b, in the absence of known genetic events linked to cetuximab resistance. MIR100HG and miR-100/125b overexpression was also observed in cetuximab-resistant colorectal cancer and head and neck squamous cell cancer cell lines and in tumors from colorectal cancer patients that progressed on cetuximab. miR-100/125b coordinately represses five Wnt/β-catenin negative regulators, resulting in increased Wnt signaling, and Wnt inhibition in cetuximab-resistant cells restored cetuximab responsiveness. We describe a double-negative feedback loop between MIR100HG and GATA6, whereby GATA6 represses MIR100HG, but this repression is relieved by miR-125b targeting of GATA6. These studies identify a clinically actionable, epigenetic cause of cetuximab resistance.

Recent advances in soft materials enable robots to possess safer human-machine interaction ways and adaptive motions, yet there remain substantial challenges to develop universal driving power sources that can achieve performance trade-offs between actuation, speed, portability, and reliability in untethered applications. Here, we introduce a class of fully soft electronic pumps that utilize electrical energy to pump liquid through electrons and ions migration mechanism. Soft pumps combine good portability with excellent actuation performances. We develop special functional liquids that merge unique properties of electrically actuation and self-healing function, providing a direction for self-healing fluid power systems. Appearances and pumpabilities of soft pumps could be customized to meet personalized needs of diverse robots. Combined with a homemade miniature high-voltage power converter, two different soft pumps are implanted into robotic fish and vehicle to achieve their untethered motions, illustrating broad potential of soft pumps as universal power sources in untethered soft robotics.

The stress‐response strategy is one of the nature's greatest developments, enabling animals and plants to respond quickly to environmental stimuli. One example is the stress‐response strategy of the Venus flytrap, which enables such a delicate plant to perceive and prey on insects at an imperceptible speed by their soft terminal lobes. Here, inspired by this unique stress‐response strategy, a soft gripper that aims at the challenges of high‐speed dynamic grasping tasks is presented. The gripper, called high‐speed soft gripper (HSG), is based on two basic design concepts. One is a snap‐through instability that enables the HSG to sense the mechanical stimuli and actuating instantly. The other one is the spider‐inspired pneumatic‐powered control system that makes the trigger process repeatable and controllable. Utilizing the stress‐response strategy, the HSG can accomplish high‐speed sensing and grasping and handle a dynamic grasping task like catching a thrown baseball. Whereas soft machines typically exhibit slow locomotion speed and low manipulation strength for the intrinsic limitations of soft materials, the exploration of the stress‐response strategy in this study can help pave the way for designing a new generation of practical high‐speed soft robots.

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