Sublimation of isolated toric focal conic domains on micro-patterned surfaces.

Toric focal conic domains (TFCDs) in smectic liquid crystals exhibit distinct topological characteristics, featuring torus-shaped molecular alignment patterns with rotational symmetry around a central core. TFCDs have attracted much interest due to their unique topological structures and properties, enabling not only fundamental studies but also potential applications in liquid crystal (LC)-based devices. Here, we investigated the precise spatial control of the arrangement of TFCDs using micropatterns and sublimation of TFCDs to estimate the energy states of the torus-like structures. Through simulations, we observed that the arrangement of TFCDs strongly depends on the shape of the topographies of underlying substrates. To accurately estimate the energetic effects of non-zero eccentricity and evaluate their thermodynamic stability, we propose a geometric model. Our findings provide valuable insights into the behavior of smectic LCs, offering opportunities for developing novel LC-based devices with precise control over their topological properties.

Sidewinder-Inspired Self-Adjusting, Lateral-Rolling Soft Robots for Autonomous Terrain Exploration.

Helical structures of liquid crystal elastomers (LCEs) hold promise in soft robotics for self-regulated rolling motions. The understanding of their motion paths and potentials for terrain exploration remains limited. This study introduces a self-adjusting, lateral-rolling soft robot inspired by sidewinder snakes. The spring-like LCE helical filaments (HFs) autonomously respond to thermal cues, demonstrating dynamic and sustainable locomotion with adaptive rolling along non-linear paths. By fine-tuning the diameter, pitch, and modulus of the LCE HFs, and the environmental temperature, the movements of the LCE HFs, allowing for exploration of diverse terrains over a 600 cm2 area within a few minutes, can be programmed. LCE HFs are showcased to navigate through over nine obstacles, including maze escaping, terrain exploration, target hunting, and successfully surmounting staircases through adaptable rolling.

Endogenous renal adiponectin drives gluconeogenesis through enhancing pyruvate and fatty acid utilization.

Adiponectin is a secretory protein, primarily produced in adipocytes. However, low but detectable expression of adiponectin can be observed in cell types beyond adipocytes, particularly in kidney tubular cells, but its local renal role is unknown. We assessed the impact of renal adiponectin by utilizing male inducible kidney tubular cell-specific adiponectin overexpression or knockout mice. Kidney-specific adiponectin overexpression induces a doubling of phosphoenolpyruvate carboxylase expression and enhanced pyruvate-mediated glucose production, tricarboxylic acid cycle intermediates and an upregulation of fatty acid oxidation (FAO). Inhibition of FAO reduces the adiponectin-induced enhancement of glucose production, highlighting the role of FAO in the induction of renal gluconeogenesis. In contrast, mice lacking adiponectin in the kidney exhibit enhanced glucose tolerance, lower utilization and greater accumulation of lipid species. Hence, renal adiponectin is an inducer of gluconeogenesis by driving enhanced local FAO and further underlines the important systemic contribution of renal gluconeogenesis.

Protective roles of adiponectin and molecular signatures of HNF4α and PPARα as downstream targets of adiponectin in pancreatic ß cells.

The disease progression of the metabolic syndrome is associated with prolonged hyperlipidemia and insulin resistance, eventually giving rise to impaired insulin secretion, often concomitant with hypoadiponectinemia. As an adipose tissue derived hormone, adiponectin is beneficial for insulin secretion and ß cell health and differentiation. However, the down-stream pathway of adiponectin in the pancreatic islets has not been studied extensively. Here, along with the overall reduction of endocrine pancreatic function in islets from adiponectin KO mice, we examine PPARα and HNF4α as additional down-regulated transcription factors during a prolonged metabolic challenge. To elucidate the function of ß cell-specific PPARα and HNF4α expression, we developed doxycycline inducible pancreatic ß cell-specific PPARα (ß-PPARα) and HNF4α (ß-HNF4α) overexpression mice. ß-PPARα mice exhibited improved protection from lipotoxicity, but elevated ß-oxidative damage in the islets, and also displayed lowered phospholipid levels and impaired glucose-stimulated insulin secretion. ß-HNF4α mice showed a more severe phenotype when compared to ß-PPARα mice, characterized by lower body weight, small islet mass and impaired insulin secretion. RNA-sequencing of the islets of these models highlights overlapping yet unique roles of ß-PPARα and ß-HNF4α. Given that ß-HNF4α potently induces PPARα expression, we define a novel adiponectin-HNF4α-PPARα cascade. We further analyzed downstream genes consistently regulated by this axis. Among them, the islet amyloid polypeptide (IAPP) gene is an important target and accumulates in adiponectin KO mice. We propose a new mechanism of IAPP aggregation in type 2 diabetes through reduced adiponectin action.

Autonomous, untethered gait-like synchronization of lobed loops made from liquid crystal elastomer fibers via spontaneous snap-through.

The transition from one equilibrium state to another via rapid snap-through can store elastic energy and release it as kinetic energy for rapid motion as seen in Venus flytrap and hummingbird to catch insects mid-flight. They are explored in soft robotics for repeated and autonomous motions. In this study, we synthesize curved liquid crystal elastomer (LCE) fibers as the building blocks that can undergo buckling instability upon heated on a hot surface, leading to autonomous snap-through and rolling behaviors. When they are connected into lobed loops, where each fiber is geometrically constrained by the neighboring ones, they demonstrate autonomous, self-regulated, and repeated synchronization with a frequency of ~1.8 Hz. By adding a rigid bead on the fiber, we can fine-tune the actuation direction and speed (up to ~2.4 mm/s). Last, we demonstrate various gait-like locomotion patterns using the loops as the robot's legs.

Versatile Mechanochromic Sensor based on Highly Stretchable Chiral Liquid Crystalline Elastomer.

A mechanochromic strain sensor that is capable of distinguishing the orientation, the location, and the degree of deformation based on the highly stretchable membrane of main-chain chiral liquid crystalline elastomer (MCLCE) is proposed. The MCLCE film is designed to exhibit uniform and significant color shift upon the small strain by using step-growth polymerization of liquid crystal (LC) oligomer and its phase-stabilization in solvent mesogen. As conformally placed on the bottom elastomer sheet, the MCLCE film shows multimodal, instantaneous color change for sensing arbitrary in-plane deformation, out-of-plane bending, and nonzero Gaussian deformation. Based on high freedom in the device design, it is also demonstrated that this sensor can display color patterns or encrypted images in response to the localized weight or strain. The simple and straightforward concept proposed here can be applicable in the fields of wearable devices, displays, and soft robotics.

Self-Folding Liquid Crystal Network Filaments Patterned with Vertically Aligned Mesogens.

Fibrous soft actuators with high molecular anisotropy are of interest for shape morphing from 1D to 2D and 3D in response to external stimuli with high actuation efficiency. Nevertheless, few have fabricated fibrous actuators with controlled molecular orientations and stiffness. Here, we fabricate filaments from liquid crystal networks (LCNs) with segmental crosslinking density and gradient porosity from a mixture of di-acrylate mesogenic monomers and small-molecule nematic or smectic liquid crystals (LCs) filled in a capillary. During photopolymerization, phase separation between the small-molecule LCs and LCN occurs, making one side of the filament considerably denser than the other side. To direct its folding mode (bending or twisting), we control the alignment of LC molecules within the capillary, either along or perpendicular to the filament long axis. We show that the direction of UV exposure can determine the direction of phase separation, which in turn direct the deformation of the filament after removal of the small-molecule LCs. We find that the vertical alignment of LCs within the filament is essential to efficiently direct bending deformation. By photopatterning the filament with segmental crosslinking density, we can induce a reversible folding/unfolding into 2D and 3D geometries triggered by deswelling/swelling in an organic solvent. Moreover, by taking advantage of the large elastic modulus of LCNs and large contrast of the modulus before and after swelling, we show that the self-folded LCP filament could act as a strong gripper.

Adipocyte mesenchymal transition contributes to mammary tumor progression.

Obesity is associated with increased cancer incidence and progression. However, the relationship between adiposity and cancer remains poorly understood at the mechanistic level. Here, we report that adipocytes from tumor-invasive mammary fat undergo de-differentiation to fibroblast-like precursor cells during tumor progression and integrate into the tumor microenvironment. Single-cell sequencing reveals that these de-differentiated adipocytes lose their original identities and transform into multiple cell types, including myofibroblast- and macrophage-like cells, with their characteristic features involved in immune response, inflammation, and extracellular matrix remodeling. The de-differentiated cells are metabolically distinct from tumor-associated fibroblasts but exhibit comparable effects on tumor cell proliferation. Inducing de-differentiation by Xbp1s overexpression promotes tumor progression despite lower adiposity. In contrast, promoting lipid-storage capacity in adipocytes through MitoNEET overexpression curbs tumor growth despite greater adiposity. Collectively, the metabolic interplay between tumor cells and adipocytes induces adipocyte mesenchymal transition and contributes to reconfigure the stroma into a more tumor-friendly microenvironment.

Elastic Instability of Cubic Blue Phase Nano Crystals in Curved Shells.

Many crystallization processes, including biomineralization and ice-freezing, occur in small and curved volumes, where surface curvature can strain the crystal, leading to unusual configurations and defect formation. The role of curvature on crystallization, however, remains poorly understood. Here, we study the crystallization of blue phase (BP) liquid crystals under curved confinement, which provides insights into the mechanism by which BPs reconfigure their three-dimensional lattice structure to adapt to curvature. BPs are a three-dimensional assembly of high-chirality liquid crystal molecules arranged into body-centered (BPI) or simple cubic (BPII) symmetries. BPs with submicrometer cubic-crystalline lattices exhibit tunable Bragg reflection and submillisecond response time to external stimuli such as an electric field, making them attractive for advanced photonic materials. In this work, we have systematically studied BPs confined in spherical shells with well-defined curvature and boundary conditions. The optical behavior of shells has also been examined at room temperature, where the cholesteric structure forms. In the cholesteric phase, perpendicular anchoring generates focal conic domains on the shell's surface, which transition into stripe patterns as the degree of curvature increases. Our results demonstrate that both higher degrees of curvature and strong spatial confinement destabilize BPI and reconfigure that phase to adopt the structure and optical features of BPII. We also show that the coupling of curvature and confinement nucleates skyrmions at greater thicknesses than those observed for a flat geometry. These findings are particularly important for integrating BPs into miniaturized and curved/flexible devices, including flexible displays, wearable sensors, and smart fabrics.

Functional Characterization of lncRNA152 as an Angiogenesis-Inhibiting Tumor Suppressor in Triple-Negative Breast Cancers.

Long noncoding RNAs have been implicated in many of the hallmarks of cancer. Herein, we found that the expression of lncRNA152 (lnc152; a.k.a. DRAIC), which we annotated previously, is highly upregulated in luminal breast cancer (LBC) and downregulated in triple-negative breast cancer (TNBC). Knockdown of lnc152 promotes cell migration and invasion in LBC cell lines. In contrast, ectopic expression of lnc152 inhibits growth, migration, invasion, and angiogenesis in TNBC cell lines. In mice, lnc152 inhibited the growth of TNBC cell xenografts, as well as metastasis of TNBC cells in an intracardiac injection model. Transcriptome analysis of the xenografts indicated that lnc152 downregulates genes controlling angiogenesis. Using pull down assays followed by LC/MS-MS, we identified RBM47, a known tumor suppressor in breast cancer, as a lnc152-interacting protein. The effects of lnc152 in TNBC cells are mediated, in part, by regulating the expression of RBM47. Collectively, our results demonstrate that lnc152 is an angiogenesis-inhibiting tumor suppressor that attenuates the aggressive cancer-related phenotypes found in TNBC. IMPLICATIONS: This study identifies lncRNA152 as an angiogenesis-inhibiting tumor suppressor that attenuates the aggressive cancer-related phenotypes found in TNBC by upregulating the expression of the tumor suppressor RBM47. As such, lncRNA152 may serve as a biomarker to track aggressiveness of breast cancer, as well as therapeutic target for treating TNBC.

Broadband and pixelated camouflage in inflating chiral nematic liquid crystalline elastomers.

Living organisms such as fishes1, cephalopods2 and clams3 are cryptically coloured with a wide range of hues and patterns for camouflage, signalling or energy regulation. Despite extensive efforts to create colour-changing materials and devices4, it is challenging to achieve pixelated structural coloration with broadband spectral shifts in a compact space. Here, we describe pneumatically inflating thin membranes of main-chain chiral nematic liquid crystalline elastomers that have such properties. By taking advantage of the large elasticity anisotropy and Poisson's ratio (>0.5) of these materials, we geometrically program the size and the layout of the encapsulated air channels to achieve colour shifting from near-infrared to ultraviolet wavelengths with less than 20% equi-biaxial transverse strain. Each channel can be individually controlled as a colour 'pixel' to match with surroundings, whether periodically or irregularly patterned. These soft materials may find uses in distinct applications such as cryptography, adaptive optics and soft robotics.

Obesity, Diabetes, and Increased Cancer Progression.

Rates of obesity and diabetes have increased significantly over the past decades and the prevalence is expected to continue to rise further in the coming years. Many observations suggest that obesity and diabetes are associated with an increased risk of developing several types of cancers, including liver, pancreatic, endometrial, colorectal, and post-menopausal breast cancer. The path towards developing obesity and diabetes is affected by multiple factors, including adipokines, inflammatory cytokines, growth hormones, insulin resistance, and hyperlipidemia. The metabolic abnormalities associated with changes in the levels of these factors in obesity and diabetes have the potential to significantly contribute to the development and progression of cancer through the regulation of distinct signaling pathways. Here, we highlight the cellular and molecular pathways that constitute the links between obesity, diabetes, cancer risk and mortality. This includes a description of the existing evidence supporting the obesity-driven morphological and functional alternations of cancer cells and adipocytes through complex interactions within the tumor microenvironment.

Reversible Curvature Reversal of Monolithic Liquid Crystal Elastomer Film and Its Smart Valve Application.

Beyond a traditional stimuli-responsive soft actuator that shows a single motion by a stimulus, multidirectional actuation reversal with a single stimulus is highly required in applications such as shape morphing sensors and soft robotics. Liquid crystal elastomers (LCEs) are one of the most attractive candidates for the soft actuator due to their capability of stimuli-responsive shape changing in 3D, which is programmable with local orientation of LC mesogens. Here, a simple but effective method to fabricate monolithic LCE actuators that are capable of reversible curvature reversal in bending and twisting deformation by a single stimulus-heat-is reported. The curvature reversal of the LCE film can be programmed by means of asymmetric crosslinking density along the thickness and the orientation of the LC mesogens. The curvature reversal of the monolithic LCE film exhibits highly reversible (more than 100 times) and fast actuation (≈3-5 s) by heating and cooling, allowing new concept of a practical application using LCE material: a self-regulated smart valve that is capable of qualitatively sorting liquids by temperature. It is believed that this system is potentially applied to a self-regulated sorting platform for various endothermic and exothermic chemical or biological reactions.

Alternate therapeutic pathways for PARP inhibitors and potential mechanisms of resistance.

Homologous recombination (HR) repair deficiency impairs the proper maintenance of genomic stability, thus rendering cancer cells vulnerable to loss or inhibition of DNA repair proteins, such as poly(ADP-ribose) polymerase-1 (PARP-1). Inhibitors of nuclear PARPs are effective therapeutics for a number of different types of cancers. Here we review key concepts and current progress on the therapeutic use of PARP inhibitors (PARPi). PARPi selectively induce synthetic lethality in cancer cells with homologous recombination deficiencies (HRDs), the most notable being cancer cells harboring mutations in the BRCA1 and BRCA2 genes. Recent clinical evidence, however, shows that PARPi can be effective as cancer therapeutics regardless of BRCA1/2 or HRD status, suggesting that a broader population of patients might benefit from PARPi therapy. Currently, four PARPi have been approved by the Food and Drug Administration (FDA) for the treatment of advanced ovarian and breast cancer with deleterious BRCA mutations. Although PARPi have been shown to improve progression-free survival, cancer cells inevitably develop resistance, which poses a significant obstacle to the prolonged use of PARP inhibitors. For example, somatic BRCA1/2 reversion mutations are often identified in patients with BRCA1/2-mutated cancers after treatment with platinum-based therapy, causing restoration of HR capacity and thus conferring PARPi resistance. Accordingly, PARPi have been studied in combination with other targeted therapies to overcome PARPi resistance, enhance PARPi efficacy, and sensitize tumors to PARP inhibition. Moreover, multiple clinical trials are now actively underway to evaluate novel combinations of PARPi with other anticancer therapies for the treatment of PARPi-resistant cancer. In this review, we highlight the mechanisms of action of PARP inhibitors with or without BRCA1/2 defects and provide an overview of the ongoing clinical trials of PARPi. We also review the current progress on PARPi-based combination strategies and PARP inhibitor resistance.

Specific Binding of snoRNAs to PARP-1 Promotes NAD+-Dependent Catalytic Activation.

Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant and ubiquitous nuclear enzyme that catalyzes the transfer of ADP-ribose from donor NAD+ molecules to specific amino acids on substrate proteins. The catalytic activity of PARP-1 has long been known to be allosterically stimulated by the free ends of DNA, such as those found at double-strand breaks in the genome. A number of studies have also shown that the catalytic activity of PARP-1 can also be stimulated by various types of RNA. A recent study by Nakamoto et al., however, has contradicted these results, concluding that the apparent stimulatory activity of the RNAs was due to contaminating DNA in the RNA preparations used in the biochemical assays. Here we show using a carefully controlled set of biochemical assays that DNA-free, in vitro-transcribed, PARP-1-interacting snoRNAs can stimulate PARP-1 catalytic activity. We confirmed the activation of PARP-1 by snoRNAs using a chemically synthesized snoRNA, as well as CRISPR/Cas9-mediated knockout of snoRNAs in cells. Finally, we provide a set of considerations and experimental conditions for the careful evaluation of RNA-stimulated PARP-1 catalytic activity that will help researchers avoid artifacts.

PARPs and ADP-ribosylation in RNA biology: from RNA expression and processing to protein translation and proteostasis.

ADP-ribosylation (ADPRylation) is a posttranslational modification of proteins discovered nearly six decades ago, but many important questions remain regarding its molecular functions and biological roles, as well as the activity of the ADP-ribose (ADPR) transferase enzymes (PARP family members) that catalyze it. Growing evidence indicates that PARP-mediated ADPRylation events are key regulators of the protein biosynthetic pathway, leading from rDNA transcription and ribosome biogenesis to mRNA synthesis, processing, and translation. In this review we describe the role of PARP proteins and ADPRylation in all facets of this pathway. PARP-1 and its enzymatic activity are key regulators of rDNA transcription, which is a critical step in ribosome biogenesis. An emerging role of PARPs in alternative splicing of mRNAs, as well as direct ADPRylation of mRNAs, highlight the role of PARP members in RNA processing. Furthermore, PARP activity, stimulated by cellular stresses, such as viral infections and ER stress, leads to the regulation of mRNA stability and protein synthesis through posttranscriptional mechanisms. Dysregulation of PARP activity in these processes can promote disease states. Collectively, these results highlight the importance of PARP family members and ADPRylation in gene regulation, mRNA processing, and protein abundance. Future studies in these areas will yield new insights into the fundamental mechanisms and a broader utility for PARP-targeted therapeutic agents.

Threading the Spindle: A Geometric Study of Chiral Liquid Crystal Polymer Microparticles.

Polymeric particles are strong candidates for designing artificial materials capable of emulating the complex twisting-based functionality observed in biological systems. In this Letter, we provide the first detailed investigation of the swelling behavior of bipolar polymer liquid crystalline microparticles. Deswelling from the spherical bipolar configuration causes the microparticles to contract anisotropically and twist in the process, resulting in a twisted spindle-shaped structure. We propose a model to describe the observed spiral patterns and twisting behavior.

Programming emergent symmetries with saddle-splay elasticity.

The director field adopted by a confined liquid crystal is controlled by a balance between the externally imposed interactions and the liquid's internal orientational elasticity. While the latter is usually considered to resist all deformations, liquid crystals actually have an intrinsic propensity to adopt saddle-splay arrangements, characterised by the elastic constant [Formula: see text]. In most realisations, dominant surface anchoring treatments suppress such deformations, rendering [Formula: see text] immeasurable. Here we identify regimes where more subtle, patterned surfaces enable saddle-splay effects to be both observed and exploited. Utilising theory and continuum calculations, we determine experimental regimes where generic, achiral liquid crystals exhibit spontaneously broken surface symmetries. These provide a new route to measuring [Formula: see text]. We further demonstrate a multistable device in which weak, but directional, fields switch between saddle-splay-motivated, spontaneously-polar surface states. Generalising beyond simple confinement, our highly scalable approach offers exciting opportunities for low-field, fast-switching optoelectronic devices which go beyond current technologies.

Self-Regulated Smectic Emulsion with Switchable Lasing Application.

A structurally reversible smectic liquid crystal (LC) emulsion made of semifluorinated rod-type molecules in silicon oil, which is controlled by simple heating and cooling, is presented. Without adding any kind of additives, such as surfactants, polymers or emulsifiers, and without using any special tools, such as microfluidics or gas bubbling, the LC molecules spontaneously form monodisperse spherical and myelin-like structures upon cooling from the isotropic temperature. The LC emulsion can easily trap guest materials, providing a platform for repeatable and reliable switchable emulsification. For example, this interesting system enables the realization of an on-off lasing system by confining fluorescent dyes in the LC droplets.