NicE-C efficiently reveals open chromatin-associated chromosome interactions at high resolution.

Enhancer-promoter communication is known to regulate spatiotemporal dynamics of gene expression. Several methods are available to capture enhancer-promoter interactions, but they either require large amounts of starting materials and are costly, or provide a relative low resolution in chromatin contact maps. Here, we present nicking enzyme-assisted open chromatin interaction capture (NicE-C), a method that leverages nicking enzyme-mediated open chromatin profiling and chromosome conformation capture to enable robust and cost-effective detection of open chromatin interactions at high resolution, especially enhancer-promoter interactions. Using TNF stimulation and mouse kidney aging as models, we applied NicE-C to reveal characteristics of dynamic enhancer-promoter interactions.

A Bibliometric Analysis of the Spatial Transcriptomics Literature from 2006 to 2023.

In recent years, spatial transcriptomics (ST) research has become a popular field of study and has shown great potential in medicine. However, there are few bibliometric analyses in this field. Thus, in this study, we aimed to find and analyze the frontiers and trends of this medical research field based on the available literature. A computerized search was applied to the WoSCC (Web of Science Core Collection) Database for literature published from 2006 to 2023. Complete records of all literature and cited references were extracted and screened. The bibliometric analysis and visualization were performed using CiteSpace, VOSviewer, Bibliometrix R Package software, and Scimago Graphica. A total of 1467 papers and reviews were included. The analysis revealed that the ST publication and citation results have shown a rapid upward trend over the last 3 years. Nature Communications and Nature were the most productive and most co-cited journals, respectively. In the comprehensive global collaborative network, the United States is the country with the most organizations and publications, followed closely by China and the United Kingdom. The author Joakim Lundeberg published the most cited paper, while Patrik L. Ståhl ranked first among co-cited authors. The hot topics in ST are tissue recognition, cancer, heterogeneity, immunotherapy, differentiation, and models. ST technologies have greatly contributed to in-depth research in medical fields such as oncology and neuroscience, opening up new possibilities for the diagnosis and treatment of diseases. Moreover, artificial intelligence and big data drive additional development in ST fields.

Strong, tough and conductive single-network hydrogels based on deswelling and the salting-out effect.

In recent years, the continuous attention given to increasing the fracture toughness and Young's modulus of polymeric gels has gradually shifted from toughening strategies on double-network (DN) gels to single-network (SN) gels. The salt-soaking method has been adopted to realize the toughening of SN gels through the salting-out effect and deswelling, constructing dense network structures with simultaneously precipitated polymer chains and cross-links. By comparing the mechanical properties between salt-treated hydrogels and air-dried hydrogels, the increased polymer chain concentration is proved to promote energy transfer by enlarging the dissipation region size due to the unwinding and slippage of coiled chains during stretching. The newly formed cross-link points in salt-treated hydrogels are considered to consume more deformation energy during stretching. The synergistic effect in energy transfer and dissipation arising from increases in polymer fraction and cross-linking plays an indispensable role in toughening SN hydrogels. In addition, the soaking process introduces abundant free ions to endow hydrogels with prominent conductivity. Thus, this salt-soaking method provides a general approach to synthesize strong, tough and conductive hydrogels with applications in flexible electrical devices.

Strong and tough polysaccharide organohydrogels for strain, humidity and temperature sensors.

To avoid the potential toxicity of monomer residues in synthetic polymer based organohydrogels, natural polysaccharide-based organohydrogels are expected to be used in multi-functional wearable sensory systems, but most of them have unsatisfactory stiffness, strength and fracture toughness. Herein, a cooking and soaking strategy is proposed to prepare novel natural polysaccharide-based organohydrogels possessing outstanding stiffness, strength, toughness, freezing resistance, heating resistance and long-term durability. The agar organohydrogel exhibits a fracture stress of 3.3 MPa, a Young's modulus of 2.26 MPa and a fracture toughness of 14.8 kJ m-2, the κ-carrageenan organohydrogel exhibits a fracture stress of 3.3 MPa, a Young's modulus of 4.34 MPa and a fracture toughness of 11.0 kJ m-2, and the gellan organohydrogel exhibits a fracture stress of 1.2 MPa, a Young's modulus of 2.81 MPa and a fracture toughness of 5.4 kJ m-2. Furthermore, the agar organohydrogels are assembled into multi-functional wearable sensors by introducing NaCl as a conducting agent exhibiting responses to strain (5-150%), temperature (-15 to 60 °C) and humidity (11-97%), and possessing exceptional multi-sensory capabilities. Therefore, the developed strategy has shown a new pathway towards strengthening polysaccharide-based organohydrogels with potential for application in wearable sensory systems.

A strong and tough gelatin/polyvinyl alcohol double network hydrogel actuator with superior actuation strength and fast actuation speed.

Hydrogels are widely used in actuators that are applied in numerous fields such as multifunctional sensors, soft robots, artificial muscles, manipulators and microfluidic valves, and yet their applications in soft robots and artificial muscles are often limited by low actuation strength and slow actuation speed. Here, we develop a hydrogel actuator with high actuation strength (contraction strength of 850 kPa), fast actuation speed (response time of 90 s) and high energy density (output working density of 72 kJ m-3) by introducing a storing-releasing elastic potential energy method into a double network hydrogel. The high actuation strength is owing to the double network hydrogel, which possesses a high elastic modulus of 1.3 MPa, fracture strength of 1.8 MPa, and fracture energy of 16 kJ m-2. The fast actuation speed is due to the storing-releasing elastic potential energy method, which stretches the hydrogel and locks the hydrogel at deformed shape under external stimuli to store the elastic potential energy and then makes the hydrogel contract rapidly under new stimuli to release the pre-stored energy. A capture actuator and a hand muscle actuator are fabricated to achieve strong and fast actuation. The hydrogel actuator has shown potential applications in soft robots and artificial muscles.

Extremely stretchable and tough hybrid hydrogels based on gelatin, κ-carrageenan and polyacrylamide.

Nowadays, several approaches are being suggested to endow hydrogels with improved mechanical properties for practical applications as cartilage and skin replacements, soft electronics, and actuators. However, it remains a challenge to develop DN gels with both high fracture toughness and fracture stretch. Here, we introduce (bio)polyelectrolyte complexes (PECs) consisting of gelatin and κ-carrageenan as the first brittle network and covalently crosslinked polyacrylamide (PAAm) as the second stretchable network to fabricate a highly stretchable and notch-insensitive gelatin/κ-carrageenan/PAAm hydrogel. The unprecedented high stretchability (∼51.7) is ascribed to the reduction of stress concentration and defects in the network structure through the fracture of the PEC gel. In addition, a high fracture toughness (∼16053.34 J m-2) is achieved by effective energy transfer between the PECs and PAAm gel due to their covalent crosslinking, and efficient energy dissipation through destroying inter- and intramolecular interactions in the PEC gel.

Comprehensive Analysis of lncRNA and miRNA Expression Profiles and ceRNA Network Construction in Osteoporosis.

Multiple profiling studies have identified a number of non-coding RNAs associated with the pathogenesis of human diseases. However, the exact regulatory mechanisms and functions of these non-coding RNAs in the development of osteoporosis have not yet been explored. Transcriptome gene expression and miRNA microarray data from peripheral blood monocytes of five high hip bone mineral density (BMD) subjects and five low hip BMD subjects were analyzed. Differentially expressed mRNAs, lncRNAs, and miRNAs were identified and subjected to functional enrichment analysis. Additionally, protein-protein interaction (PPI), lncRNA-mRNA, and mRNA-lncRNA-miRNA competing endogenous RNA (ceRNA) networks were constructed. Differential analysis revealed that 297 mRNAs, 151 lncRNAs, and 38 miRNAs were significantly differentially expressed between peripheral blood monocytes from high and low hip BMD subjects. Key genes including ACLY, HSPA5, and AKT1 were subsequently identified in the PPI network. Additionally, differentially expressed lncRNAs were primarily enriched in the citrate cycle (TCA cycle), biosynthesis of antibiotics, and carbon metabolism pathways. Finally, the mRNA-lncRNA-miRNA network revealed several key ceRNA regulatory relationships among the transcripts and non-coding RNAs. Key mRNAs and non-coding RNAs identified in the networks represent potential biomarkers or targets in the diagnosis and management of osteoporosis. Our findings represent a resource for further functional research on the ceRNA regulation mechanism of non-coding RNA in osteoporosis.

Fully physically cross-linked double network hydrogels with strong mechanical properties, good recovery and self-healing properties.

Combining a hydrophobic interaction crosslinked curdlan as the first network and hydrophobic interaction crosslinked polyacrylamide as the second network, we have fabricated a curdlan/HPAAm double network (DN) hydrogel using a one-pot method. The resulting DN hydrogel exhibited good mechanical properties, i.e. an elastic modulus of 103 kPa, a tensile fracture strength of 0.81 MPa, a tensile stretch of 25.3 and a compressive stress of 62.5 MPa when the compressive strain increased up to 99%. The DN gel could withstand ten compression tests under 90% compressive strain without observable damage. The DN gel demonstrated 84% stiffness recovery and 97% toughness recovery after the deformed samples were relaxed and stored at 95 °C for 4 h. The stiffness and fracture stress of the DN gel were enhanced after sterilization treatment at 120 °C. Furthermore, the gels exhibited 52% self-healing of fracture stretch after the samples were cut and brought into contact at 95 °C for 4 h. The self-recovery and self-healing properties of the DN gel both originated from the first curdlan network via the reformation of hydrophobic interactions and the second HPAAm network via reformation of the broken hydrophobic associations.

Topology, Geometry, and Mechanics of Z-Plasty.

Reconstructive surgeries often use topological manipulation of tissue to minimize postoperative scarring. The most common version of this, Z-plasty, involves modifying a straight line cut into a Z shape, followed by a rotational transposition of the resulting triangular pedicle flaps, and a final restitching of the wound. This locally reorients the anisotropic stress field and reduces the potential for scarring. We analyze the planar geometry and mechanics of the Z-plasty to quantify the rotation of the overall stress field and the local forces on the restitched cut using theory, simulations, and simple physical Z-plasty experiments with foam sheets that corroborate each other. Our study rationalizes the most typical surgical choice of this angle, and opens the way for a range of surgical decisions by characterizing the stresses along the cut.

Entropic elasticity based coarse-grained model of lipid membranes.

Various models for lipid bilayer membranes have been presented to investigate their morphologies. Among them, the aggressive coarse-grained models, where the membrane is represented by a single layer of particles, are computationally efficient and of practical importance for simulating membrane dynamics at the microscopic scale. In these models, soft potentials between particle pairs are used to maintain the fluidity of membranes, but the underlying mechanism of the softening requires further clarification. We have analyzed the membrane area decrease due to thermal fluctuations, and the results demonstrate that the intraparticle part of entropic elasticity is responsible for the softening of the potential. Based on the stretching response of the membrane, a bottom-up model is developed with an entropic effect explicitly involved. The model reproduces several essential properties of the lipid membrane, including the fluid state and a plateau in the stretching curve. In addition, the area compressibility modulus, bending rigidity, and spontaneous curvature display linear dependence on model parameters. As a demonstration, we have investigated the closure and morphology evolution of membrane systems driven by spontaneous curvature, and vesicle shapes observed experimentally are faithfully reproduced.

Laser printing hierarchical structures with the aid of controlled capillary-driven self-assembly.

Capillary force is often regarded as detrimental because it may cause undesired distortion or even destruction to micro/nanostructures during a fabrication process, and thus many efforts have been made to eliminate its negative effects. From a different perspective, capillary force can be artfully used to construct specific complex architectures. Here, we propose a laser printing capillary-assisted self-assembly strategy for fabricating regular periodic structures. Microscale pillars are first produced by localized femtosecond laser polymerization and are subsequently assembled into periodic hierarchical architectures with the assistance of controlled capillary forces in an evaporating liquid. Spatial arrangements, pillar heights, and evaporation processes are readily tuned to achieve designable ordered assemblies with various geometries. Reversibility of the assembly is also revealed by breaking the balance between the intermolecular force and the elastic standing force. We further demonstrate the functionality of the hierarchical structures as a nontrivial tool for the selective trapping and releasing of microparticles, opening up a potential for the development of in situ transportation systems for microobjects.

On the growth and form of the gut.

The developing vertebrate gut tube forms a reproducible looped pattern as it grows into the body cavity. Here we use developmental experiments to eliminate alternative models and show that gut looping morphogenesis is driven by the homogeneous and isotropic forces that arise from the relative growth between the gut tube and the anchoring dorsal mesenteric sheet, tissues that grow at different rates. A simple physical mimic, using a differentially strained composite of a pliable rubber tube and a soft latex sheet is consistent with this mechanism and produces similar patterns. We devise a mathematical theory and a computational model for the number, size and shape of intestinal loops based solely on the measurable geometry, elasticity and relative growth of the tissues. The predictions of our theory are quantitatively consistent with observations of intestinal loops at different stages of development in the chick embryo. Our model also accounts for the qualitative and quantitative variation in the distinct gut looping patterns seen in a variety of species including quail, finch and mouse, illuminating how the simple macroscopic mechanics of differential growth drives the morphology of the developing gut.

Growth, geometry, and mechanics of a blooming lily.

Despite the common use of the blooming metaphor, its floral inspiration remains poorly understood. Here we study the physical process of blooming in the asiatic lily Lilium casablanca. Our observations show that the edges of the petals wrinkle as the flower opens, suggesting that differential growth drives the deployment of these laminar shell-like structures. We use a combination of surgical manipulations and quantitative measurements to confirm this hypothesis and provide a simple theory for this change in the shape of a doubly curved thin elastic shell subject to differential growth across its planform. Our experiments and theory overturn previous hypotheses that suggest that blooming is driven by differential growth of the inner layer of the petals and in the midrib by providing a qualitatively different paradigm that highlights the role of edge growth. This functional morphology suggests new biomimetic designs for deployable structures using boundary or edge actuation rather than the usual bulk or surface actuation.

Nuclear deformation and cell division of single cell on elongated micropatterned substrates fabricated by DMD lithography.

Cells sense mechanical signals from the surrounding environment and transmit them to the nucleus through mechanotransduction to regulate cellular behavior. Microcontact printing, which utilizes elastomer stamps, is an effective method for simulating the cellular microenvironment and manipulating cell morphology. However, the conventional fabrication process of silicon masters and elastomer stamps requires complex procedures and specialized equipment, which restricts the widespread application of micropatterning in cell biology and hinders the investigation of the role of cell geometry in regulating cell behavior. In this study, we present an innovative method for convenient resin stamp microfabrication based on digital micromirror device planar lithography. Using this method, we generated a series of patterns ranging from millimeter to micrometer scales and validated their effectiveness in controlling adhesion at both collective and individual cell levels. Additionally, we investigated mechanotransduction and cell behavior on elongated micropatterned substrates. We then examined the effects of cell elongation on cytoskeleton organization, nuclear deformation, focal adhesion formation, traction force generation, nuclear mechanics, and the growth of HeLa cells. Our findings reveal a positive correlation between cell length and mechanotransduction. Interestingly, HeLa cells with moderate length exhibit the highest cell division and proliferation rates. These results highlight the regulatory role of cell elongation in mechanotransduction and its significant impact on cancer cell growth. Furthermore, our methodology for controlling cell adhesion holds the potential for addressing fundamental questions in both cell biology and biomedical engineering.

Chitosan-based double network hydrogel loading herbal small molecule for accelerating wound healing.

Skin injuries are one of the most common clinical traumas worldwide, and wound dressings are considered to be one of key factors in wound healing. Natural polymer-based hydrogels have been developed as ideal materials for a new generation of dressings due to their excellent biocompatibility and wetting ability. However, the inadequate mechanical performances and lack of efficacy in promoting wound healing have limited the application of natural polymer-based hydrogels as wound dressings. In this work, a double network hydrogel based on natural chitosan molecules was constructed to enhance the mechanical properties, and emodin, a herbal natural product, was loaded into the hydrogel to improve the healing effect of the dressing. The structure of the chitosan-emodin network formed by Schiff base reaction and microcrystalline network of biocompatible polyvinyl alcohol endowed hydrogels with excellent mechanical properties and ensured its integrity as wound dressings. Moreover, the hydrogel showed excellent wound healing properties due to the loading of emodin. The hydrogel dressing could promote cell proliferation, cell migration, and secretion of growth factors. The animal experimental results also demonstrated that the hydrogel dressing facilitated the regeneration of blood vessels and collagen and accelerated wound healing.

The shape of a long leaf.

Long leaves in terrestrial plants and their submarine counterparts, algal blades, have a typical, saddle-like midsurface and rippled edges. To understand the origin of these morphologies, we dissect leaves and differentially stretch foam ribbons to show that these shapes arise from a simple cause, the elastic relaxation via bending that follows either differential growth (in leaves) or differential stretching past the yield point (in ribbons). We quantify these different modalities in terms of a mathematical model for the shape of an initially flat elastic sheet with lateral gradients in longitudinal growth. By using a combination of scaling concepts, stability analysis, and numerical simulations, we map out the shape space for these growing ribbons and find that as the relative growth strain is increased, a long flat lamina deforms to a saddle shape and/or develops undulations that may lead to strongly localized ripples as the growth strain is localized to the edge of the leaf. Our theory delineates the geometric and growth control parameters that determine the shape space of finite laminae and thus allows for a comparative study of elongated leaf morphology.

Stiff and strong hydrogel tube with great mechanical properties and high stability in various solutions.

Hydrogel tubes are widely used in fields such as artificial blood vessels, drug delivery, biomedical scaffolds and cell adhesion, yet their application is often limited by unsatisfactory mechanical properties and poor stability in various solutions. Herein, a novel hydrogel tube exhibiting a remarkable mechanical performance and stability in various solutions is prepared by introducing a dual physically cross-linked double network (DN) hydrogel matrix. The obtained hydrogel tube can withstand ∼60 N load without fracture and be stretched to over twice its original length before and after immersing in various solutions. The great mechanical properties and stability in various solutions of hydrogel tubes are due to the introduction of a dual physically cross-linked poly(acrylamide-co-acrylic acid)/carboxymethylcellulose sodium/Fe3+ DN hydrogel, which possesses high elastic modulus (3.71 MPa), fracture energy (15.4 kJ m-2), and great stability in various solutions. In addition, the hydrogel tubes with different thickness, diameters, shapes and the multiple branched hydrogel tubes can also be fabricated to enable further functionalization for application requirements. Therefore, this new type of hydrogel tube presents tremendous potential for applications in biomedical and engineering fields.

Bio-Inspired Bianisotropic Magneto-Sensitive Elastomers with Excellent Multimodal Transformation.

Magneto-sensitive soft materials that can accomplish fast, remote, and reversible shape morphing are highly desirable for practical applications including biomedical devices, soft robotics, and flexible electronics. In conventional magneto-sensitive elastomers (MSEs), there is a tradeoff between employing hard magnetic particles with costly magnetic programming and utilizing soft magnetic particle chains causing tedious and small deformation. Here, inspired by the shape and movement of mimosa, a novel soft magnetic particle doped shape material bianisotropic magneto-sensitive elastomer (SM bianisotropic MSE) with multimodal transformation and superior deformability is developed. The high-aspect-ratio shape anisotropy and the material anisotropy in which the magnetic particles are arranged in a chainlike structure together impart magnetic anisotropy to the SM bianisotropic MSE. A magneto-elastic analysis model is proposed, and it is elucidated that magnetic anisotropy leads to peculiar field-direction-dependent multimodal transformation. More importantly, a quadrilateral assembly and a regular hexagon assembly based on this SM bianisotropic MSE are designed, and they exhibit 2.4 and 1.7 times the deformation capacity of shape anisotropic samples, respectively. By exploiting the multidegree of freedom and excellent deformability of the SM bianisotropic MSE, flexible logic switches and ultrasoft magnetic manipulators are further demonstrated, which prove its potential applications in future intelligent flexible electronics and autonomous soft robotics.

Polyvinyl alcohol/gelatin hydrogels regulate cell adhesion and chromatin accessibility.

Cell adhesion has a critical influence on various processes such as cancer metastasis and wound healing. Many substrates have been used for studying cell adhesion and its related biological processes, it is still highly desirable to have a simply prepared and low-cost substrate suitable for regulating cell adhesion. In this study, we produced a series of polyvinyl alcohol/gelatin hydrogels with different gelatin concentrations via dry-annealing method. Our data showed that the protein adsorbing capability was enhanced and cell adhesion area and the ratio of non-spherical cells were increased with the increment of gelatin concentration. We also observed that varying cell adhesion conditions induced by polyvinyl alcohol /gelatin hydrogels resulted in expression level changes of genes involved in mechanotransduction from extracellular matrices (ECM) to the nucleus. In particular, we detected a widespread increase in chromatin accessibility under poor cell adhesion condition. This work provides a useful hydrogel system for regulating cell adhesion and opens up new possibilities for the design of biomaterials for cell adhesion study.

Preparation of stretchable and self-healable dual ionically cross-linked hydrogel based on chitosan/polyacrylic acid with anti-freezing property for multi-model flexible sensing and detection.

As a kind of promising material for flexible wearable electronics, conductive hydrogels have attracted extensive interests of researchers for their inherent merits such as superior mechanical properties, biocompatibility, and permeability. Herein, we constructed a new type of highly stretchable, anti-freezing, self-healable, and conductive hydrogel based on chitosan/polyacrylic acid. The large amount of ions inside the network had five functions for the proposed hydrogel, including excellent mechanical behaviors, high conductivity, self-recovery, self-healing and anti-freezing capability. Consequently, the proposed hydrogel possessed tunable stretchability (1190-1550%), tensile strength (0.96-2.56 MPa), toughness (5.7-14.7 MJ/m3), superior self-healing property (self-healing efficiency up to 83.7%), high conductivity (4.58-5.76 S/m), and excellent anti-freezing capability. To our knowledge, the self-healable hydrogel with balanced tensile strength, toughness, conductivity, and low-temperature tolerance can hardly be achieved till now. Furthermore, the conductive hydrogels exhibited high sensitivity (gauge factor up to 10.8) in a broad strain window (0-1000%) and could detect the conventional motion signals of human body such as bending of a knuckle, swallowing, and pressure signal at both room temperature and -20 °C. Moreover, the hydrogels could also be fabricated as flexible detectors to identify different temperatures, different kinds of solutions, and different concentrations of the solution.