Shape memory polymer with programmable recovery onset.

Stimulus-responsive shape-shifting polymers1-3 have shown unique promise in emerging applications, including soft robotics4-7, medical devices8, aerospace structures9 and flexible electronics10. Their externally triggered shape-shifting behaviour offers on-demand controllability essential for many device applications. Ironically, accessing external triggers (for example, heating or light) under realistic scenarios has become the greatest bottleneck in demanding applications such as implantable medical devices8. Certain shape-shifting polymers rely on naturally present stimuli (for example, human body temperature for implantable devices)8 as triggers. Although they forgo the need for external stimulation, the ability to control recovery onset is also lost. Naturally triggered, yet actively controllable, shape-shifting behaviour is highly desirable but these two attributes are conflicting. Here we achieved this goal with a four-dimensional printable shape memory hydrogel that operates via phase separation, with its shape-shifting kinetics dominated by internal mass diffusion rather than by heat transport used for common shape memory polymers8-11. This hydrogel can undergo shape transformation at natural ambient temperature, critically with a recovery onset delay. This delay is programmable by altering the degree of phase separation during device programming, which offers a unique mechanism for shape-shifting control. Our naturally triggered shape memory polymer with a tunable recovery onset markedly lowers the barrier for device implementation.

Itaconate inhibits SYK through alkylation and suppresses inflammation against hvKP induced intestinal dysbiosis.

Hypervirulent Klebsiella pneumoniae (hvKP) is a highly lethal opportunistic pathogen that elicits more severe inflammatory responses compared to classical Klebsiella pneumoniae (cKP). In this study, we investigated the interaction between hvKP infection and the anti-inflammatory immune response gene 1 (IRG1)-itaconate axis. Firstly, we demonstrated the activation of the IRG1-itaconate axis induced by hvKP, with a dependency on SYK signaling rather than STING. Importantly, we discovered that exogenous supplementation of itaconate effectively inhibited excessive inflammation by directly inhibiting SYK kinase at the 593 site through alkylation. Furthermore, our study revealed that itaconate effectively suppressed the classical activation phenotype (M1 phenotype) and macrophage cell death induced by hvKP. In vivo experiments demonstrated that itaconate administration mitigated hvKP-induced disturbances in intestinal immunopathology and homeostasis, including the restoration of intestinal barrier integrity and alleviation of dysbiosis in the gut microbiota, ultimately preventing fatal injury. Overall, our study expands the current understanding of the IRG1-itaconate axis in hvKP infection, providing a promising foundation for the development of innovative therapeutic strategies utilizing itaconate for the treatment of hvKP infections.

An Orthogonal Dynamic Covalent Polymer Network with Distinctive Topology Transformations for Shape- and Molecular Architecture Reconfiguration.

Bond exchange in a typical dynamic covalent polymer network allows access to macroscopic shape reconfigurability, but the network architecture is not altered. An alternative possibility is that the network architecture can be designed to switch to various topological states corresponding to different material properties. Achieving both in one network can expand the material scope, but their intrinsically conflicting mechanisms make it challenging. We design a dynamic covalent network that can undergo two orthogonal topological transformations, namely transesterification on the branched chains and olefin metathesis on the mainframe. This allows independent control of the macroscopic shape and molecular architecture. With this design, we illustrate a bottlebrush network with programmable shape and spatially definable mechanical properties. Our strategy paves a way to on-demand regulation of network polymers.

Are Contact Angle Measurements Useful for Oxide-Coated Liquid Metals?

This work establishes that static contact angles for gallium-based liquid metals have no utility despite the continued and common use of such angles in the literature. In the presence of oxygen, these metals rapidly form a thin (∼1-3 nm) surface oxide "skin" that adheres to many surfaces and mechanically impedes its flow. This property is problematic for contact angle measurements, which presume the ability of liquids to flow freely to adopt shapes that minimize the interfacial energy. We show here that advancing angles for a metal are always high (>140°)-even on substrates to which it adheres-because the solid native oxide must rupture in tension to advance the contact line. The advancing angle for the metal depends subtly on the substrate surface chemistry but does not vary strongly with hydrophobicity of the substrate. During receding measurements, the metal droplet initially sags as the liquid withdraws from the "sac" formed by the skin and thus the contact area with the substrate initially increases despite its volumetric recession. The oxide pins at the perimeter of the deflated "sac" on all the surfaces are tested, except for certain rough surfaces. With additional withdrawal of the liquid metal, the pinned angle gets smaller until eventually the oxide "sac" collapses. Thus, static contact angles can be manipulated mechanically from 0° to >140° due to hysteresis and are therefore uninformative. We also provide recommendations and best practices for wetting experiments, which may find use in applications that use these alloys such as soft electronics, composites, and microfluidics.

Shape Memory Polymers with Patternable Recovery Onset Regulated by Light.

Shape memory polymers (SMPs) show attractive prospects in emerging fields such as soft robots and biomedical devices. Although their typical trigger-responsive character offers the essential shape-changing controllability, having to access external stimulation is a major bottleneck toward many applications. Recently emerged autonomous SMPs exhibit unique stimuli-free shape-shifting behavior with its controllability achieved via a delayed and programmable recovery onset. Achieving multi-shape morphing in an arbitrary fashion, however, is infeasible. In this work, a molecular design that allows to spatio-temporally define the recovery onset of an autonomous shape memory hydrogel (SMH) is reported. By introducing nitrocinnamate groups onto an SMH, its crosslinking density can be adjusted by light. This affects greatly the phase separation kinetics, which is the basis for the autonomous shape memory behavior. Consequently, the recovery onset can be regulated between 0 to 85 min. With masked light, multiple recovery onsets in an arbitrarily defined pattern which correspondingly enable multi-shape morphing can be realized. This ability to achieve highly sophisticated morphing without relying on any external stimulation greatly extends the versatility of SMPs.

FASN regulates STING palmitoylation via malonyl-CoA in macrophages to alleviate sepsis-induced liver injury.

STING (stimulator of interferon genes) is a critical immunoregulatory protein in sepsis and is regulated by various mechanisms, especially palmitoylation. FASN (fatty acid synthase) is the rate-limiting enzyme to generate cellular palmitic acid (PA) via acetyl-CoA and malonyl-CoA and participates in protein palmitoylation. However, the mechanisms underlying the interaction between STING and FASN have not been completely understood. In this study, STING-knockout mice were used to confirm the pivotal role of STING in sepsis-induced liver injury. Metabolomics confirmed the dyslipidemia in septic mice and patients. The compounds library was screened, revealing that FASN inhibitors exerted a significant inhibitory effect on the STING pathway. Mechanically, the regulatory effect of FASN on the STING pathway was dependent on palmitoylation. Further experiments indicated that the upstream of FASN, malonyl-CoA inhibited STING pathway possibly due to C91 (palmitoylated residue) of STING. Overall, this study reveals a novel paradigm of STING regulation and provides a new perspective on immunity and metabolism.

High speed underwater hydrogel robots with programmable motions powered by light.

Stimuli-responsive shape-changing hydrogels are attractive candidates for use as underwater soft robots. The bottleneck lies in the low actuation speed inherently limited by the water diffusion between hydrogels and their surrounding environment. In addition, accessing complex motions is restricted by the material fabrication methods. Here we report a hitherto unknown mechanism to achieve high-speed and programmable actuations for a disulfide crosslinked thermally responsive hydrogel. The dynamic photo-activated disulfide bond exchange allows photo-mechanical programming to introduce spatio-selective network anisotropy. This gives rise to an actuation behavior dominated by thermally driven conformation change of the locally oriented polymer chains instead of the common mass-diffusion-based mechanism. With the incorporation of photothermal fillers, light-powered oscillation at frequencies as high as 1.7 Hz is realized. This, coupled with the versatility of the programming, allows access to robots with diverse high-speed motions including continuous swimming, step-wise walking, and rotating.

Orthogonal Photochemistry toward Direct Encryption of a 3D-Printed Hydrogel.

Encryption technologies are essential for information security and product anti-counterfeiting, but they are typically restricted to planar surfaces. Encryption on complex 3D objects offers great potential to further improve security. However, it is rarely achieved owing to the lack of encoding strategies for nonplanar surfaces. Here, an approach is reported to directly encrypt on a 3D-printed object employing orthogonal photochemistry. In this system, visible light photochemistry is used for 3D printing of a hydrogel, and ultraviolet light is subsequently employed to activate its geometrically complex surface through the dissociation of ortho-nitrobenzyl ester units in a spatioselective manner for information coding. This approach offers a new way for more reliable encryption, and the underlying orthogonal photochemistry can be extended toward functional modification of 3D-printed products beyond information protection.

Precise Orchestration of Gasdermins' Pore-Forming Function by Posttranslational Modifications in Health and Disease.

Gasdermins (GSDMs) serve as pivotal executors of pyroptosis and play crucial roles in host defence, cytokine secretion, innate immunity, and cancer. However, excessive or inappropriate GSDMs activation is invariably accompanied by exaggerated inflammation and results in tissue damage. In contrast, deficient or impaired activation of GSDMs often fails to promptly eliminate pathogens, leading to the increasing severity of infections. The activity of GSDMs requires meticulous regulation. The dynamic modulation of GSDMs involves many aspects, including autoinhibitory structures, proteolytic cleavage, lipid binding and membrane translocation (oligomerization and pre-pore formation), oligomerization (pore formation) and pore removal for membrane repair. As the most comprehensive and efficient regulatory pathway, posttranslational modifications (PTMs) are widely implicated in the regulation of these aspects. In this comprehensive review, we delve into the complex mechanisms through which a variety of proteases cleave GSDMs to enhance or hinder their function. Moreover, we summarize the intricate regulatory mechanisms of PTMs that govern GSDMs-induced pyroptosis.

Upcycling of dynamic thiourea thermoset polymers by intrinsic chemical strengthening.

Thermoset polymers are indispensable but their environmental impact has been an ever-increasing concern given their typical intractability. Although concepts enabling their reprocessing have been demonstrated, their practical potential is limited by the deteriorated performance of the reprocessed materials. Here, we report a thiourea based thermoset elastomer that can be reprocessed with enhanced mechanical properties. We reveal that the thiourea bonds are dynamic which leads to the reprocessibility. More importantly, they can undergo selective oxidation during high temperature reprocessing, resulting in significant chemical strengthening within certain reprocessing cycles. This is opposite to most polymers for which reprocessing typically results in material deterioration. The possibility of having materials with inherent reprocessing induced performance enhancement points to a promising direction towards polymer recycling.

Homeostatic growth of dynamic covalent polymer network toward ultrafast direct soft lithography.

Soft lithography is a complementary extension of classical photolithography, which involves a multistep operation that is environmentally unfriendly and intrinsically limited to planar surfaces. Inspired by homeostasis processes in biology, we report a self-growth strategy toward direct soft lithography, bypassing conventional photolithography and its limitations. Our process uses a paraffin swollen light responsive dynamic polymer network. Selective light exposure activates the network locally, causing stress imbalance. This drives the internal redistribution of the paraffin liquid, yielding controllable formation of microstructures. This single-step process is completed in 10 seconds, does not involve any volatile solvents/reactants, and can be adapted to three-dimensional complex surfaces. The living nature of the network further allows sequential growth of hierarchical microstructures. The versatility and efficiency of our approach offer possibilities for future nanotechnologies beyond conventional microfabrication techniques.

Differential diffusion driven far-from-equilibrium shape-shifting of hydrogels.

Far-from-equilibrium (FFE) conditions give rise to many unusual phenomena in nature. In contrast, synthetic shape-shifting materials typically rely on monotonic evolution between equilibrium states, limiting inherently the richness of the shape-shifting behaviors. Here we report an unanticipated shape-shifting behavior for a hydrogel that can be programmed to operate FFE-like behavior. During its temperature triggered shape-shifting event, the programmed stress induces uneven water diffusion, which pushes the hydrogel off the equilibrium based natural pathway. The resulting geometric change enhances the diffusion contrast in return, creating a self-amplifying sequence that drives the system into an FFE condition. Consequently, the hydrogel exhibits counterintuitive two opposite shape-shifting events under one single stimulation, at a speed accelerated by more than one order magnitude. Our discovery points to a future direction in creating FFE conditions to access otherwise unattainable shape-shifting behaviors, with potential implications for many engineering applications including soft robotics and medical devices.

On demand shape memory polymer via light regulated topological defects in a dynamic covalent network.

The ability to undergo bond exchange in a dynamic covalent polymer network has brought many benefits not offered by classical thermoplastic and thermoset polymers. Despite the bond exchangeability, the overall network topologies for existing dynamic networks typically cannot be altered, limiting their potential expansion into unexplored territories. By harnessing topological defects inherent in any real polymer network, we show herein a general design that allows a dynamic network to undergo rearrangement to distinctive topologies. The use of a light triggered catalyst further allows spatio-temporal regulation of the network topology, leading to an unusual opportunity to program polymer properties. Applying this strategy to functional shape memory networks yields custom designable multi-shape and reversible shape memory characteristics. This molecular principle expands the design versatility for network polymers, with broad implications in many other areas including soft robotics, flexible electronics, and medical devices.

4D Printing of a Digital Shape Memory Polymer with Tunable High Performance.

Shape memory polymers (SMP) with 3D geometries and tunable shape-shifting behavior can open up new opportunities in intelligent devices. Achieving both simultaneously is difficult for conventional approaches. 4D printing allows fabrication of complex 3D SMP geometries that can change shapes (i.e., the fourth dimension is time), but tuning the shape memory response is challenging because of the printing constraints. Here, we report a material and process concept that allows digital light fabrication of SMP with fine control of not only the geometries but also the shape memory characteristics, within a printing time of 30 s. Digital light modulation allows spatio-temporal tuning of the material properties including shape memory transition temperature, rubbery modulus, and maximum elongation (up to 250%). Consequently, the process allows producing multiple-SMP within a single material construct using the same printing precursor. We demonstrate that this unique attribute is beneficial in constructing unusual shape-shifting 3D nano-photonic and electronic devices. The simplicity and versatility of our approach facilitates its future expansion into a wide range of geometrically complex devices with advanced functions.

1-Hydroxy-3-[(E)-4-(piperazine-diium)but-2-enyloxy]-9,10-anthraquinone ditrifluoroactate induced autophagic cell death in human PC3 cells.

The autophagy of human prostate cancer cells (PC3 cells) induced by a new anthraquinone derivative, 1-Hydroxy-3-[(E)-4-(piperazine-diium)but-2-enyloxy]-9,10-anthraquinone ditrifluoroactate (PA) was investigated, and the relationship between autophagy and reactive oxygen species (ROS) generation was studied. The results indicated that PA induced PC3 cell death in a time- and dose-dependent manner, could inhibit PC3 cell growth by G1 phase cell cycle arrest and corresponding decrease in the G2/M cell population and induced S-phase arrest accompanied by a significant decrease G2/M and G1 phase numbers after PC3 cells treated with PA for 48 h, and increased the accumulation of autophagolysosomes and microtubule-associated protein LC3-ll, a marker of autophagy. However, these phenomenon were not observed in the group pretreated with the autophagy inhibitor 3-MA or Bafilomycin A1 (BAF), suggesting that PA induced PC3 cell autophagy. In addition, we found that PA triggered ROS generation in cells, while the levels of ROS decreased in the N-acetylcysteine (NAC) co-treatment, indicating that PA-mediated autophagy was partly blocked by NAC. In summary, the autophagic cell death of human PC3 cells mediated by PA-triggered ROS generation.