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Abstract Bone is a dynamic mineralized tissue that undergoes continuous turnover throughout life. While the general mechanism of bone mineral metabolism is documented, the role of underlying collagen structures in regulating osteoblastic mineral deposition and osteoclastic mineral resorption remains an active research area, partly due to the lack of biomaterial platforms supporting accurate and analytical investigation. The recently introduced osteoid-inspired demineralized bone paper (DBP), prepared by 20-μm thin sectioning of demineralized bovine compact bone, holds promise in addressing this challenge as it preserves the intrinsic bony collagen structure and retains semi-transparency. Here, we report on the impact of collagen structures on modulating osteoblast and osteoclast-driven bone mineral metabolism using vertical and transversal DBPs that exhibit a uniaxially aligned and a concentric ring collagen structure, respectively. Translucent DBP reveals these collagen structures and facilitates longitudinal tracking of mineral deposition and resorption under brightfield microscopy for at least 3 wk. Genetically labeled primary osteogenic cells allow fluorescent monitoring of these cellular processes. Osteoblasts adhere and proliferate following the underlying collagen structures of DBPs. Osteoblastic mineral deposition is significantly higher in vertical DBP than in transversal DBP. Spatiotemporal analysis reveals notably more osteoblast adhesion and faster mineral deposition in vascular regions than in bone regions. Subsequent osteoclastic resorption follows these mineralized collagen structures, directing distinct trench and pit-type resorption patterns. In vertical DBP, trench-type resorption occurs at an 80% frequency, whereas transversal DBP shows 35% trench-type and 65% pit-type resorption. Our studies substantiate the importance of collagen structures in regulating mineral metabolism by osteogenic cells. DBP is expected to serve as an enabling biomaterial platform for studying various aspects of cellular and extracellular bone remodeling biology. 

Abstract Osteoclasts are the primary target for osteoporosis drug development. Recent animal studies revealed the crucial roles of osteoblasts in regulating osteoclastogenesis and the longer lifespans of osteoclasts than previously thought with fission and recycling. However, existing culture platforms are limited to replicating these newly identified cellular processes. We report a demineralized bone paper (DBP)-based osteoblast culture and osteoclast assay platform that replicates osteoclast fusion, fission, resorption, and apoptosis with high fidelity and analytical power. An osteoid-inspired DBP supports rapid and structural mineral deposition by osteoblasts. Coculture osteoblasts and bone marrow monocytes under biochemical stimulation recapitulate osteoclast differentiation and function. The DBP-based bone model allows longitudinal quantitative fluorescent monitoring of osteoclast responses to bisphosphonate drug, substantiating significantly reducing their number and lifespan. Finally, we demonstrate the feasibility of humanizing the bone model. The DBP-based osteo assay platforms are expected to advance bone remodeling-targeting drug development with improved prediction of clinical outcomes. 

We have grown and characterized (110)-oriented YBa2Cu3O7−x (YBCO)/PrBa2(Cu0.8Ga0.2)3O7−x (PBCGO) bilayer and YBCO/PBCGO/YBCO trilayer heterostructures, which were deposited by pulsed laser deposition technique for the nanofabrication of (110)-oriented YBCO-based superconductor (S)/insulator (I)/superconductor (S) tunneling vertical geometry Josephson junction and other superconductor electronic devices. The structural properties of these heterostructures, investigated through various x-ray diffraction techniques (profile, x-ray reflectivity, pole figure, and reciprocal mapping), showed (110)-oriented epitaxial growth with a preferred c-axis-in-plane direction for all layers of the heterostructures. The atomic force microscopy measurement on the top surface of the heterostructures showed crack-free and pinhole-free, compact surface morphology with about a few nanometer root mean square roughness over the 5 × 5 μm2 region. The electrical resistivity measurements on the (110)-direction of the heterostructures showed superconducting critical temperature (Tc) values above 77 K and a very small proximity effect due to the interfacial contact of the superconducting YBCO layers with the PBCGO insulating layer. Raman spectroscopy measurements on the heterostructures showed the softening of the Ag-type Raman modes associated with the apical oxygen O(4) and O(2)-O(3)-in-phase vibrations compared to the stand-alone (110)-oriented PBCGO due to the residual stress and additional two Raman modes at ∼600 and ∼285 cm−1 frequencies due to the disorder at the Cu–O chain site of the PBCGO. The growth process and structural, electrical transport, and Raman spectroscopy characterization of (110)-oriented YBCO/PBCGO bilayer and YBCO/PBCGO/YBCO trilayer heterostructures are discussed in detail. 

Purple bacteria and their less known applicationsJungwoo Lee, High-School Student, and Arpita Bose, Associate Professor at Washington University in St. Louis, guide us through purple bacteria and their less-known applications, including wastewater treatment and biofertilization. Purple bacteria, also known as purple photosynthetic bacteria, which belong to the phylum Proteobacteria, can be classified into purple sulfur bacteria (PSB) and purple non-sulfur bacteria (PNSB). In contrast to PSB, PNSB demonstrate the ability to utilize various electron donors and acceptors, which further expands their applications. Their adaptable metabolism, coupled with well-defined genetic manipulation techniques, positions PNSB as ideal models for elucidating the intricacies of metabolic pathways, which hold significant implications for diverse biotechnological applications, including wastewater treatment, and as biofertilizers. 

Chemoresistance is a significant problem in the effective treatment of bone metastasis. Adipocytes are a major stromal cell type in the bone marrow and may play a crucial role in developing microenvironment-driven chemoresistance. However, detailed investigation remains challenging due to the anatomical inaccessibility and intrinsic tissue complexity of the bone marrow microenvironment. In this study, we developed 2D and 3D in vitro models of bone marrow adipocytes to examine the mechanisms underlying adipocyte-induced chemoresistance. We first established a protocol for the rapid and robust differentiation of human bone marrow stromal cells (hBMSCs) into mature adipocytes in 2D tissue culture plastic using rosiglitazone (10 μM), a PPARγ agonist. Next, we created a 3D adipocyte culture model by inducing aggregation of hBMSCs and adipogenesis to create adipocyte spheroids in porous hydrogel scaffolds that mimic bone marrow sinusoids. Simulated chemotherapy treatment with doxorubicin (2.5 μM) demonstrated that mature adipocytes sequester doxorubicin in lipid droplets, resulting in reduced cytotoxicity. Lastly, we performed direct coculture of human multiple myeloma cells (MM1.S) with the established 3D adipocyte model in the presence of doxorubicin. This resulted in significantly accelerated multiple myeloma proliferation following doxorubicin treatment. Our findings suggest that the sequestration of hydrophobic chemotherapeutics by mature adipocytes represents a potent mechanism of bone marrow microenvironment-driven chemoresistance. 

In a traditional distributed storage system, a source can be restored perfectly when a certain subset of servers is contacted. The coding is independent of the contents of the source. This paper considers instead a lossy source coding version of this problem where the more servers that are contacted, the higher the quality of the restored source. An example could be video stored on distributed storage. In information theory, this is called the multiple description problem, where the distortion depends on the number of descriptions received. The problem considered in this paper is how to restore the system operation when one of the servers fail and a new server replaces it, that is, repair. The requirement is that the distortions in the restored system should be no more than in the original system. The question is how many extra bits are needed for repair. We find an achievable rate and show that this is optimal in certain cases. One conclusion is that it is necessary to design the multiple description codes with repair in mind; just using an existing multiple description code results in unnecessary high repair rates.