Pharmacologic or genetic interference with atrogene signaling protects against glucocorticoid-induced musculoskeletal and cardiac disease.

Despite their beneficial actions as immunosuppressants, glucocorticoids (GC) have devastating effects on the musculoskeletal and cardiac systems, as long-term treated patients exhibit high incidence of falls, bone fractures, and cardiovascular events. Herein, we show that GC upregulate simultaneously in bone, skeletal muscle, and the heart the expression of E3 ubiquitin ligases (atrogenes), known to stimulate the proteasomal degradation of proteins. Activation of vitamin D receptor (VDR) signaling with the VDR ligands calcitriol or eldecalcitol prevented GC-induced atrogene upregulation in vivo and ex vivo in bone/muscle organ cultures and preserved tissue structure/mass and function of the 3 tissues in vivo.

Aging impairs the osteocytic regulation of collagen integrity and bone quality.

Poor bone quality is a major factor in skeletal fragility in elderly individuals. The molecular mechanisms that establish and maintain bone quality, independent of bone mass, are unknown but are thought to be primarily determined by osteocytes. We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling (PLR), which maintains bone material properties.

Dynamic Structural Change of Plant Epidermal Cell Walls under Strain.

The molecular foundations of epidermal cell wall mechanics are critical for understanding structure-function relationships of primary cell walls in plants and facilitating the design of bioinspired materials. To uncover the molecular mechanisms regulating the high extensibility and strength of the cell wall, the onion epidermal wall is stretched uniaxially to various strains and cell wall structures from mesoscale to atomic scale are characterized. Upon longitudinal stretching to high strain, epidermal walls contract in the transverse direction, resulting in a reduced area.

Type 2 diabetes impairs annulus fibrosus fiber deformation and rotation under disc compression in the University of California Davis type 2 diabetes mellitus (UCD-T2DM) rat model.

Understanding the biomechanical behavior of the intervertebral disc is crucial for studying disease mechanisms and developing tissue engineering strategies for managing disc degeneration. We used synchrotron small-angle X-ray scattering to investigate how changes to collagen behavior contribute to alterations in the disc's ability to resist compression. Coccygeal motion segments from 6-month-old lean Sprague-Dawley rats ( ) and diabetic obese University of California Davis type 2 diabetes mellitus (UCD-T2DM) rats ( , diabetic for days) were compressed during simultaneous synchrotron scanning to measure collagen strain at the nanoscale (beamline 7.

Dimorphic Mechanisms of Fragility in Diabetes Mellitus: the Role of Reduced Collagen Fibril Deformation.

Diabetes mellitus (DM) is an emerging metabolic disease, and the management of diabetic bone disease poses a serious challenge worldwide. Understanding the underlying mechanisms leading to high fracture risk in DM is hence of particular interest and urgently needed to allow for diagnosis and treatment optimization. In a case-control postmortem study, the whole 12th thoracic vertebra and cortical bone from the mid-diaphysis of the femur from male individuals with type 1 diabetes mellitus (T1DM) (n = 6; 61.

Nanolattice-Forming Hybrid Collagens in Protective Shark Egg Cases.

Nanoscopic structural control with long-range ordering remains a profound challenge in nanomaterial fabrication. The nanoarchitectured egg cases of elasmobranchs rely on a hierarchically ordered latticework for their protective function─serving as an exemplary system for nanoscale self-assembly. Although the proteinaceous precursors are known to undergo intermediate liquid crystalline phase transitions before being structurally arrested in the final nanolattice architecture, their sequences have so far remained unknown.

Distinguishing Gas-Phase and Nanoparticle Contributions to Small-Angle X-ray Scattering in Reacting Aerosol Flows.

We have developed a strategy for distinguishing between small-angle X-ray scattering (SAXS) from gas-phase species and newly formed nanoparticles in mixed gas- and particle-phase reacting flows. This methodology explicitly accounts for temperature-dependent scattering from gases. We measured SAXS in a sooting linear laminar partially premixed co-flow ethylene/air diffusion flame.

Nanolatticed Architecture Mitigates Damage in Shark Egg Cases.

Structural versatility and multifunctionality of biological materials have resulted in countless bioinspired strategies seeking to emulate the properties of nature. The nanostructured egg case of swell sharks is one of the toughest permeable membranes known and, thus, presents itself as a model system for materials where the conflicting properties, strength and porosity, are desirable. The egg case possesses an intricately ordered structure that is designed to protect delicate embryos from the external environment while enabling respiratory and metabolic exchange, achieving a tactical balance between conflicting properties.

Dynamic Structure and Phase Behavior of a Block Copolymer Electrolyte under dc Polarization.

An important consideration when designing lithium battery electrolytes for advanced applications is how the electrolyte facilitates ion transport at fast charge and discharge rates. Large current densities are accompanied by large salt concentration gradients across the electrolyte. Nanostructured composite electrolytes have been proposed to enable the use of high energy density lithium metal anodes, but many questions about the interplay between the electrolyte morphology and the salt concentration gradient that forms under dc polarization remain unanswered.

On the Origins of Fracture Toughness in Advanced Teleosts: How the Swordfish Sword's Bone Structure and Composition Allow for Slashing under Water to Kill or Stun Prey.

The osseous sword of a swordfish () is specialized to incapacitate prey with stunning blows. Considering the sword's growth and maturation pattern, aging from the sword's base to the tip, while missing a mechanosensitive osteocytic network, an in-depth understanding of its mechanical properties and bone quality is lacking. Microstructural, compositional, and nanomechanical characteristics of the bone along the sword are investigated to reveal structural mechanisms accounting for its exceptional mechanical competence.

Chronic kidney disease and aging differentially diminish bone material and microarchitecture in C57Bl/6 mice.

Chronic kidney disease (CKD) is a common disease of aging and increases fracture risk over advanced age alone. Aging and CKD differently impair bone turnover and mineralization. We thus hypothesize that the loss of bone quality would be greatest with the combination of advanced age and CKD.

Mechanical Competence and Bone Quality Develop During Skeletal Growth.

Bone fracture risk is influenced by bone quality, which encompasses bone's composition as well as its multiscale organization and architecture. Aging and disease deteriorate bone quality, leading to reduced mechanical properties and higher fracture incidence. Largely unexplored is how bone quality and mechanical competence progress during longitudinal bone growth.

Contributions of Material Properties and Structure to Increased Bone Fragility for a Given Bone Mass in the UCD-T2DM Rat Model of Type 2 Diabetes.

Adults with type 2 diabetes (T2D) have a higher fracture risk for a given bone quantity, but the mechanisms remain unclear. Using a rat model of polygenic obese T2D, we demonstrate that diabetes significantly reduces whole-bone strength for a given bone mass (μCT-derived BMC), and we quantify the roles of T2D-induced deficits in material properties versus bone structure; ie, geometry and microarchitecture. Lumbar vertebrae and ulnae were harvested from 6-month-old lean Sprague-Dawley rats, obese Sprague-Dawley rats, and diabetic obese UCD-T2DM rats (diabetic for 69 ± 7 days; blood glucose >200 mg/dL).

Note: Setup for chemical atmospheric control during in situ grazing incidence X-ray scattering of printed thin films.

In order to tailor the assembling of polymers and organic molecules, a deeper understanding of the kinetics involved in thin film production is necessary. While post-production characterization only provides insight on the final film structure, more sophisticated experimental setups are needed to probe the structure formation processes in situ during deposition. The drying kinetics of a deposited organic thin film strongly influences the assembling process on the nanometer scale.

In situ dynamic observations of perovskite crystallisation and microstructure evolution intermediated from [PbI] cage nanoparticles.

Hybrid lead halide perovskites have emerged as high-performance photovoltaic materials with their extraordinary optoelectronic properties. In particular, the remarkable device efficiency is strongly influenced by the perovskite crystallinity and the film morphology. Here, we investigate the perovskites crystallisation kinetics and growth mechanism in real time from liquid precursor continually to the final uniform film.

Printing Fabrication of Bulk Heterojunction Solar Cells and In Situ Morphology Characterization.

Polymer-based materials hold promise as low-cost, flexible efficient photovoltaic devices. Most laboratory efforts to achieve high performance devices have used devices prepared by spin coating, a process that is not amenable to large-scale fabrication. This mismatch in device fabrication makes it difficult to translate quantitative results obtained in the laboratory to the commercial level, making optimization difficult.

Intrinsic mechanical behavior of femoral cortical bone in young, osteoporotic and bisphosphonate-treated individuals in low- and high energy fracture conditions.

Bisphosphonates are a common treatment to reduce osteoporotic fractures. This treatment induces osseous structural and compositional changes accompanied by positive effects on osteoblasts and osteocytes. Here, we test the hypothesis that restored osseous cell behavior, which resembles characteristics of younger, healthy cortical bone, leads to improved bone quality.

Ordering in Polymer Micelle-Directed Assemblies of Colloidal Nanocrystals.

Assembly of presynthesized nanocrystals by block copolymer micelles can be rationalized by the incorporation of nanocrystals into micellar coronas of constant width. As determined by quantitative analysis using small-angle X-ray scattering, high loading of small nanocrystals yields composites exhibiting order on two length scales, whereas intermediate loading of nanocrystals larger than the coronal width produces single nanocrystal networks. The resulting structures obey expectations of thermodynamically driven assembly on the nanocrystal length scale, whereas kinetically frozen packing principles dictate order on the polymer micelle length scale.

Alendronate treatment alters bone tissues at multiple structural levels in healthy canine cortical bone.

Bisphosphonates are widely used to treat osteoporosis, but have been associated with atypical femoral fractures (AFFs) in the long term, which raises a critical health problem for the aging population. Several clinical studies have suggested that the occurrence of AFFs may be related to the bisphosphonate-induced changes of bone turnover, but large discrepancies in the results of these studies indicate that the salient mechanisms responsible for any loss in fracture resistance are still unclear. Here the role of bisphosphonates is examined in terms of the potential deterioration in fracture resistance resulting from both intrinsic (plasticity) and extrinsic (shielding) toughening mechanisms, which operate over a wide range of length-scales.

On the tear resistance of skin.

Tear resistance is of vital importance in the various functions of skin, especially protection from predatorial attack. Here, we mechanistically quantify the extreme tear resistance of skin and identify the underlying structural features, which lead to its sophisticated failure mechanisms. We explain why it is virtually impossible to propagate a tear in rabbit skin, chosen as a model material for the dermis of vertebrates.

Fast printing and in situ morphology observation of organic photovoltaics using slot-die coating.

The mini-slot-die coater offers a simple, convenient, materials-efficient route to print bulk-heterojunction (BHJ) organic photovoltaics (OPVs) that show efficiencies similar to spin-coating. Grazing-incidence X-ray diffraction (GIXD) and GI small-angle X-ray scattering (GISAXS) methods are used in real time to characterize the active-layer formation during printing. A polymer-aggregation-phase-separation-crystallization mechanism for the evolution of the morphology describes the observations.

Effect of sequential treatments with alendronate, parathyroid hormone (1-34) and raloxifene on cortical bone mass and strength in ovariectomized rats.

Unlabelled: Anti-resorptive and anabolic agents are often prescribed for the treatment of osteoporosis continuously or sequentially for many years. However their impact on cortical bone quality and bone strength is not clear.

Methods: Six-month old female rats were either sham operated or ovariectomized (OVX).

Protective role of Arapaima gigas fish scales: structure and mechanical behavior.

The scales of the arapaima (Arapaima gigas), one of the largest freshwater fish in the world, can serve as inspiration for the design of flexible dermal armor. Each scale is composed of two layers: a laminate composite of parallel collagen fibrils and a hard, highly mineralized surface layer. We review the structure of the arapaima scales and examine the functions of the different layers, focusing on the mechanical behavior, including tension and penetration of the scales, with and without the highly mineralized outer layer.

Fracture resistance of human cortical bone across multiple length-scales at physiological strain rates.

While most fracture-mechanics investigations on bone have been performed at low strain rates, physiological fractures invariably occur at higher loading rates. Here, at strain rates from 10(-5) to 10(-1) s(-1), we investigate deformation and fracture in bone at small length-scales using in situ small-angle x-ray scattering (SAXS) to study deformation in the mineralized collagen fibrils and at the microstructural level via fracture-mechanics experiments to study toughening mechanisms generating toughness through crack-tip shielding. Our results show diminished bone toughness at increasing strain rates as cracks penetrate through the osteons at higher strain rates instead of deflecting at the cement lines, which is a prime toughening mechanism in bone at low strain rates.