Cargo specificity, regulation, and therapeutic potential of cytoplasmic dynein.

Intracellular retrograde transport in eukaryotic cells relies exclusively on the molecular motor cytoplasmic dynein 1. Unlike its counterpart, kinesin, dynein has a single isoform, which raises questions about its cargo specificity and regulatory mechanisms. The precision of dynein-mediated cargo transport is governed by a multitude of factors, including temperature, phosphorylation, the microtubule track, and interactions with a family of activating adaptor proteins. Activating adaptors are of particular importance because they not only activate the unidirectional motility of the motor but also connect a diverse array of cargoes with the dynein motor. Therefore, it is unsurprising that dysregulation of the dynein-activating adaptor transport machinery can lead to diseases such as spinal muscular atrophy, lower extremity, and dominant. Here, we discuss dynein motor motility within cells and in in vitro, and we present several methodologies employed to track the motion of the motor. We highlight several newly identified activating adaptors and their roles in regulating dynein. Finally, we explore the potential therapeutic applications of manipulating dynein transport to address diseases linked to dynein malfunction.

Polymorphic Self-Assembly with Procedural Flexibility for Monodisperse Quaternary Protein Structures of DegQ Enzymes.

As large molecular tertiary structures, some proteins can act as small robots that find, bind, and chaperone target protein clients, showing the potential to serve as smart building blocks in self-assembly fields. Instead of using such intrinsic functions, most self-assembly methodologies for proteins aim for de novo-designed structures with accurate geometric assemblies, which can limit procedural flexibility. Here, a strategy enabling polymorphic clustering of quaternary proteins, exhibiting simplicity and flexibility of self-assembling paths for proteins in forming monodisperse quaternary cage particles is presented. It is proposed that the enzyme protomer DegQ, previously solved at low resolution, may potentially be usable as a threefold symmetric building block, which can form polyhedral cages incorporated by the chaperone action of DegQ in the presence of protein clients. To obtain highly monodisperse cage particles, soft, and hence, less resistive client proteins, which can program the inherent chaperone activity of DegQ to efficient formations of polymorphic cages, depending on the size of clients are utilized. By reconstructing the atomic resolution cryogenic electron microscopy DegQ structures using obtained 12- and 24-meric clusters, the polymorphic clustering of DegQ enzymes is validated in terms of soft and rigid domains, which will provide effective routes for protein self-assemblies with procedural flexibility.

Natural Shaping of Acellular Dermal Matrices for Implant-Based Breast Reconstruction via Expansile Kirigami.

To complete a successful and aesthetic breast reconstruction for breast cancer survivors, tissue reinforcing acellular dermal matrices (ADMs) are widely utilized to create slings/pockets to keep breast implants or autologous tissue transfer secured against the chest wall in the desired location. However, ADM sheets are 2D and cannot completely cover the entire implant without wrinkles. Here, guided by finite element modeling, a kirigami strategy is presented to cut the ADM sheets with locally and precisely controlled stretchability, curvature, and elasticity. Upon expansion, a single kirigami ADM sheet can conformably wrap the implant regardless of the shape and size, forming a natural teardrop shape; contour cuts prescribe the topographical height and fractal cuts in the center ensures horizontal expandability and thus conformability. This kirigami ADM can provide support to the reconstructed breast in the desired regions, potentially offering optimal outcomes and patient-specific reconstruction, while minimizing operative time and cost.

Multiscale landscaping of droplet wettability on fibrous layers of facial masks.

Liquid mobility is ubiquitous in nature, with droplets emerging at all size scales, and artificial surfaces have been designed to mimic such mobility over the past few decades. Meanwhile, millimeter-sized droplets are frequently used for wettability characterization, even with facial mask applications, although these applications have a droplet-size target range that spans from millimeters to aerosols measuring less than a few micrometers. Unlike large droplets, microdroplets can interact sensitively with the fibers they contact with and are prone to evaporation. However, wetting behaviors at the single-microfiber level remain poorly understood. Herein, we characterized the wettability of fibrous layers, which revealed that a multiscale landscape of droplets ranged from the millimeter to the micrometer scale. The contact angle (CA) values of small droplets on pristine fibrous media showed sudden decrements, especially on a single microfiber, owing to the lack of air cushions for the tiny droplets. Moreover, droplets easily adhered to the pristine layer during droplet impact tests and then yielding widespread areas of contamination on the microfibers. To resolve this, we carved nanowalls on the pristine fibers by plasma etching, which effectively suppressed such wetting phenomena. Significantly, the resulting topographies of the microfibers managed the dynamic wettability of droplets at the multiscale, which reduced the probability of contamination with impact droplets and suppressed the wetting transition upon evaporation. These findings for the dynamic wettability of fibrous media will be useful in the fight against infectious droplets.

Influence of production systems on phenolic characteristics and antioxidant capacity of highbush blueberry cultivars.

Blueberry is a crop grown worldwide due to the excellent quality and high polyphenol content of its fruit and tolerance to cold conditions. We investigated the influence of three production systems, namely an open field, heated greenhouse, and non-heated (plastic) greenhouse, on the phenolic characteristics (total phenolic, flavonoid, and anthocyanin content) and antioxidant capacities of "Spartan" (northern highbush), "Sharpblue" (southern highbush), and "O'Neal" (southern highbush) blueberry cultivars. The non-heated production system showed the highest phenolic characteristics and antioxidant capacity in "Spartan" and "O'Neal," while the open field production system showed the highest phenolic characteristics and antioxidant capacity in "Sharpblue." Derivatives of delphinidin and malvidin were two of the most abundant anthocyanins. The heated greenhouse production system resulted in larger amounts of delphinidin derivatives compared with the other production systems, while the blueberry grown in the non-heated greenhouse produced larger amount of malvidin derivatives. The anthocyanin profiles varied according to production system and blueberry cultivars. The principal component analysis loading plot of blueberries for individual anthocyanins explained over 95% of the total variance. In summary, the results of this study suggest that a strategic approach to blueberry production could elevate the phenolic content and antioxidant capacity of cultivated blueberry. PRACTICAL APPLICATION: The highbush blueberry, a rich source of bioactive polyphenols, is a popular fruit. The microclimate of the production system of highbush blueberries affects the concentrations of antioxidative phenolic compounds such as anthocyanins. Therefore, discovering and applying the appropriate method of production for each blueberry cultivar could facilitate production of high-quality blueberries rich in phenolic antioxidants.

Physiochemical properties, dietary fibers, and functional characterization of three yuzu cultivars at five harvesting times.

This research focused on physiochemical and nutritional properties and functional characterization of three cultivars of yuzu-Native, Tadanishiki yuzu, and Namhae1-during different seasons. According to the cultivar and harvest time, yuzu cultivars were analyzed for free sugar, dietary fiber, hesperidin, naringin, and flavonoid content as well as antioxidant and antihypertensive activity. During November, Namhae1 exhibited the highest fruit weight, °Brix/acidity ratio, and total dietary fiber content. Tadanishiki contained the highest fructose and sucrose levels, pectin and cellulose contents, and soluble dietary fiber. Tadanishiki also had the highest hesperidin content in October, while the naringin content and antioxidant activity were the greatest in November. Antihypertensive activity was also the strongest for Tadanishiki, which was picked in October and November. These results indicated that Tadanishiki in October or November was the best for consumption or favorable processing because of its excellent product quality and high levels of nutritional and functional compounds.

Clogged water bridges for fog harvesting.

Capillary water bridges clogged in the holes of mesh-type fog harvesters have previously been considered only as a drawback because they decrease fog-harvesting yield by hindering airflow in front of the clogged mesh in the usual wind conditions. In this study, we show that the role of a clogged water bridge may not be entirely negative and can contribute to increased fog harvesting by increasing the effective shade coefficient in a special condition with high fog inertia. As the fog speed close to the mesh or the plate increases, clogged mesh as well as the impermeable solid plate are found to produce high fog-harvesting efficiency owing to the high inertia of fog particles that impact the blocked wall. For fast fog speeds (∼4 m s-1) near the mesh, our results show that the fog-harvesting efficiency is proportional to the effective shade coefficient because fog flow circumventing the mesh is limited owing to high fog inertia. We analyzed the clogging effect on fog-harvesting performance by distinguishing between self-clogging and non-self-clogging patterns based on the water bridge stability clogged in mesh holes.

Three-Dimensional Photoengraving of Monolithic, Multifaceted Metasurfaces.

Metasurfaces present a potent platform to manipulate light by the spatial arrangement of sub-wavelength patterns with well-defined sizes and geometries, in thin films. Metasurfaces by definition are planar. However, it would be highly desirable to integrate metasurfaces with diverse, spatially programmed sub-wavelength features into a 3D monolith, to manipulate light within a compact 3D space. Here, a 3D photoengraving strategy is presented; that is, generation of such composite metasurfaces from a single microstructure via the irradiation of multiple interference laser beams onto different facets of the parent azopolymeric microstructure. Through "photofluidization," this technique enables independent inscription and erasing of metasurfaces onto and from individual facets of 3D monoliths with arbitrary shapes and dimensions, in a high-throughput fashion (over approximately a few cm2 at a time). By engraving discrete sub-wavelength 1D surface relief gratings of different pitches on different facets of an inverse pyramidal array, a multiplexing structure-color filter is demonstrated.

Pentamidine Inhibits Titanium Particle-Induced Osteolysis In Vivo and Receptor Activator of Nuclear Factor-κB Ligand-Mediated Osteoclast Differentiation In Vitro.

Background: Wear debris-induced osteolysis leads to periprosthetic loosening and subsequent prosthetic failure. Since excessive osteoclast formation is closely implicated in periprosthetic osteolysis, identification of agents to suppress osteoclast formation and/or function is crucial for the treatment and prevention of wear particle-induced bone destruction. In this study, we examined the potential effect of pentamidine treatment on titanium (Ti) particle-induced osteolysis, and receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. Methods: The effect of pentamidine treatment on bone destruction was examined in Ti particle-induced osteolysis mouse model. Ti particles were implanted onto mouse calvaria, and vehicle or pentamidine was administered for 10 days. Then, calvarial bone tissue was analyzed using micro-computed tomography and histology. We performed in vitro osteoclastogenesis assay using bone marrow-derived macrophages (BMMs) to determine the effect of pentamidine on osteoclast formation. BMMs were treated with 20 ng/mL RANKL and 10 ng/mL macrophage colony-stimulating factor in the presence or absence of pentamidine. Osteoclast differentiation was determined by tartrate-resistant acid phosphatase staining, real-time polymerase chain reaction, and immunofluorescence staining. Results: Pentamidine administration decreased Ti particle-induced osteoclast formation significantly and prevented bone destruction compared to the Ti particle group in vivo. Pentamidine also suppressed RANKL-induced osteoclast differentiation and actin ring formation markedly, and inhibited the expression of nuclear factor of activated T cell c1 and osteoclast-specific genes in vitro. Additionally, pentamidine also attenuated RANKL-mediated phosphorylation of IκBα in BMMs. Conclusion: These results indicate that pentamidine is effective in inhibiting osteoclast formation and significantly attenuates wear debris-induced bone loss in mice.

Intrinsically reversible superglues via shape adaptation inspired by snail epiphragm.

Adhesives are ubiquitous in daily life and industrial applications. They usually fall into one of two classes: strong but irreversible (e.g., superglues) or reversible/reusable but weak (e.g., pressure-sensitive adhesives and biological and biomimetic surfaces). Achieving both superstrong adhesion and reversibility has been challenging. This task is particularly difficult for hydrogels that, because their major constituent is liquid water, typically do not adhere strongly to any material. Here, we report a snail epiphragm-inspired adhesion mechanism where a polymer gel system demonstrates superglue-like adhesion strength (up to 892 N⋅cm-2) that is also reversible. It is applicable to both flat and rough target surfaces. In its hydrated state, the softened gel conformally adapts to the target surface by low-energy deformation, which is locked upon drying as the elastic modulus is raised from hundreds of kilopascals to ∼2.3 GPa, analogous to the action of the epiphragm of snails. We show that in this system adhesion strength is based on the material's intrinsic, especially near-surface, properties and not on any near-surface structure, providing reversibility and ease of scaling up for practical applications.

Electroactive Soft Photonic Devices for the Synesthetic Perception of Color and Sound.

Color, as perceived through the eye, transcends mere information in the visible range of electromagnetism and serves as an agent for communication and entertainment. Mechanochromic systems have thus far only aimed at satisfying the sense of vision and have overlooked the possibility of generating acoustic vibrations in concert with their visual color responses that would enable the simultaneous satisfaction of the auditory system. Transcending the boundaries of the two senses (i.e., sound and color), herein a strategy for their concurrent and synesthetic fulfillment is elucidated by electrically actuating an organogel photonic device, controlled by a single input signal. This new class of devices that integrate a color module with a speaker is fabricated from a mechanochromic layer that comprises close-packed photonic lattice with an organogel matrix pervading the void fraction. Exploiting a dielectric elastomer actuator, the system's mechanical response permits the simultaneous, yet independent, exploration of visible-light reflection alongside audible sound-wave generation. Large areal strains at low frequencies of actuation tune the photonic stop-band, whereas the layer remains incompressible and exhibits negligible strain when actuated at higher frequencies (e.g., tens of Hz), thereby making it amenable to modulate sound and color simultaneously yet independently.

Thickness-independent capacitance of vertically aligned liquid-crystalline MXenes.

The scalable and sustainable manufacture of thick electrode films with high energy and power densities is critical for the large-scale storage of electrochemical energy for application in transportation and stationary electric grids. Two-dimensional nanomaterials have become the predominant choice of electrode material in the pursuit of high energy and power densities owing to their large surface-area-to-volume ratios and lack of solid-state diffusion1,2. However, traditional electrode fabrication methods often lead to restacking of two-dimensional nanomaterials, which limits ion transport in thick films and results in systems in which the electrochemical performance is highly dependent on the thickness of the film1-4. Strategies for facilitating ion transport-such as increasing the interlayer spacing by intercalation5-8 or introducing film porosity by designing nanoarchitectures9,10-result in materials with low volumetric energy storage as well as complex and lengthy ion transport paths that impede performance at high charge-discharge rates. Vertical alignment of two-dimensional flakes enables directional ion transport that can lead to thickness-independent electrochemical performances in thick films11-13. However, so far only limited success11,12 has been reported, and the mitigation of performance losses remains a major challenge when working with films of two-dimensional nanomaterials with thicknesses that are near to or exceed the industrial standard of 100 micrometres. Here we demonstrate electrochemical energy storage that is independent of film thickness for vertically aligned two-dimensional titanium carbide (Ti3C2T x ), a material from the MXene family (two-dimensional carbides and nitrides of transition metals (M), where X stands for carbon or nitrogen). The vertical alignment was achieved by mechanical shearing of a discotic lamellar liquid-crystal phase of Ti3C2T x . The resulting electrode films show excellent performance that is nearly independent of film thickness up to 200 micrometres, which makes them highly attractive for energy storage applications. Furthermore, the self-assembly approach presented here is scalable and can be extended to other systems that involve directional transport, such as catalysis and filtration.

Inhibitory effects of methyl-3,5-di-O-caffeoyl-epi-quinate on RANKL-induced osteoclast differentiation.

In this study, we have shown that methyl-3,5-di-O-caffeoyl-epi-quinate, a naturally occurring compound isolated from Ainsliaea acerifolia, inhibits receptor activator of nuclear factor-κB ligand (RANKL)-induced formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and the expression of osteoclast marker genes. Methyl-3,5-di-O-caffeoyl-epi-quinate also inhibited RANKL-induced activation of p38, Akt and extracellular signal-regulated kinase (ERK) as well as the expression of nuclear factor of activated T-cell (NFATc1), the key regulator of osteoclast differentiation. Negative regulators for osteoclast differentiation was upregulated by methyl-3,5-di-O-caffeoyl-epi-quinate. Collectively, our results suggested that methyl-3,5-di-O-caffeoyl-epi-quinate suppresses osteoclast differentiation via downregulation of RANK signaling pathways and NFATc1.

Shaping micro-clusters via inverse jamming and topographic close-packing of microbombs.

Designing topographic clusters is of significant interest, yet it remains challenging as they often lack mobility or deformability. Here we exploit the huge volumetric expansion (up to 3000%) of a new type of building block, thermally expandable microbombs. They consist of a viscoelastic polymeric shell and a volatile gas core, which, within structural confinement, create micro-clusters via inverse jamming and topographical close-packing. Upon heating, microbombs anchored in rigid confinement underwent balloon-like blowing up, allowing for dense clusters via soft interplay between viscoelastic shells. Importantly, the confinement is unyielding against the internal pressure of the microbombs, thereby enabling self-assembled clusters, which can be coupled with topographic inscription to introduce structural hierarchy on the clusters. Our strategy provides densely packed yet ultralight clusters with a variety of complex shapes, cleavages, curvatures, and hierarchy. In turn, these clusters will enrich our ability to explore the assemblies of the ever-increasing range of microparticle systems.Self-assembled systems are normally composed of incompressible building blocks, which constrain their space filling efficiency. Yu et al. show programmable, densely packed clusters using thermally expandable soft microparticles, whereby the self-assembling process is realized via a jamming transition.

Multidirectional Wrinkle Patterns Programmed by Sequential Uniaxial Strain with Conformal yet Nontraceable Masks.

Surface wrinkling is a promising route to control the mechanical, electrical, and optical properties of materials in a wide range of applications. However, previous artificial wrinkles are restricted to single or random orientation and lacks selectivity. To address this challenge, this study presents multidirectional wrinkle patterns with high selectivity and orientation through sequential uniaxial strain with conformal polymeric shadow masks. The conformal but nontraceable polymeric stencil with microapertures are adhered to a flat substrate prior to oxidation, which forms discrete and parallel wrinkles in confined domains without any contamination. By fully investigating the process, this study displays compound topography of wrinkles consisting of wrinkle islands and surrounding secondary wrinkles on the same surface. With this topography, various diffusion properties are presented: from semi-transparent yet diffusive films to multidirectional diffusive films, which will be available for new types of optical diffuser applications.

Confined Assemblies of Colloidal Particles with Soft Repulsive Interactions.

We investigate the microconfinement of charged silica nanoparticles dispersed in refractive index matching monomers in poly(dimethylsiloxane) (PDMS) porous membrane. Here, the silica colloidal particles interact with each other and the pore wall via electrostatic double layer forces. Different from the hard sphere systems where the assembled morphologies are prescribed by the diameter ratio between the cylindrical confinement and the nanoparticles, here we observe a much richer variety of assemblies that are highly sensitive to both bulk and local nanoparticle concentration with fixed particle size and channel size. The experimentally observed assembly morphologies are consistent with theoretical predictions from the literature, based on Yukawa potential in the low packing density regime. Also, most of the configurations found in the experiment are well described by computer simulations using pairwise additive long-range repulsive interactions, demonstrating the ability to control the system to obtain a desired structure.

Multifurcation Assembly of Charged Aerosols and Its Application to 3D Structured Gas Sensors.

Multifurcated assemblies composed of charged nanoparticles (NPs) are fabricated by using spark discharge and manipulating the electric field. The multifurcated structure of the assembly of NPs and spontaneous interconnections between the near structures are described. The gas sensor with the tetrafurcated-NP-assembled structure demonstrates ≈200% enhanced response to 100 ppm CO at 300 °C.

Nonlinear Frameworks for Reversible and Pluripotent Wetting on Topographic Surfaces.

Soft, ultrathin frameworks nonlinearly organized in tandem are presented to realize both reversible and pluripotent wetting on topographic surfaces. A design rule is introduced by establishing and proving the theoretical model upon hierarchical textures. Nonlinear frameworks can be conformally and reversibly wet upon complex topography in nature, thereby overcoming the wetting problems in previous conventional solid systems.

Multiplex lithography for multilevel multiscale architectures and its application to polymer electrolyte membrane fuel cell.

The production of multiscale architectures is of significant interest in materials science, and the integration of those structures could provide a breakthrough for various applications. Here we report a simple yet versatile strategy that allows for the LEGO-like integrations of microscale membranes by quantitatively controlling the oxygen inhibition effects of ultraviolet-curable materials, leading to multilevel multiscale architectures. The spatial control of oxygen concentration induces different curing contrasts in a resin allowing the selective imprinting and bonding at different sides of a membrane, which enables LEGO-like integration together with the multiscale pattern formation. Utilizing the method, the multilevel multiscale Nafion membranes are prepared and applied to polymer electrolyte membrane fuel cell. Our multiscale membrane fuel cell demonstrates significant enhancement of performance while ensuring mechanical robustness. The performance enhancement is caused by the combined effect of the decrease of membrane resistance and the increase of the electrochemical active surface area.

Microfluidic platforms with monolithically integrated hierarchical apertures for the facile and rapid formation of cargo-carrying vesicles.

We fabricated a simple yet robust microfluidic platform with monolithically integrated hierarchical apertures. This platform showed efficient diffusive mixing of the introduced lipids through approximately 8000 divisions with tiny pores (~5 µm in diameter), resulting in massive, real-time production of various cargo-carrying particles via multi-hydrodynamic focusing.