Dietary fat and bile juice, but not obesity, are responsible for the increase in small intestinal permeability induced through the suppression of tight junction protein expression in LETO and OLETF rats

<p>Abstract</p> <p>Background</p> <p>An increase in the intestinal permeability is considered to be associated with the inflammatory tone and development in the obesity and diabetes, however, the pathogenesis of the increase in the intestinal permeability is poorly understood. The present study was performed to determine the influence of obesity itself as well as dietary fat on the increase in intestinal permeability.</p> <p>Methods</p> <p>An obese rat strain, Otsuka Long Evans Tokushima Fatty (OLETF), and the lean counter strain, Long Evans Tokushima Otsuka (LETO), were fed standard or high fat diets for 16 weeks. Glucose tolerance, intestinal permeability, intestinal tight junction (TJ) proteins expression, plasma bile acids concentration were evaluated. In addition, the effects of rat bile juice and dietary fat, possible mediators of the increase in the intestinal permeability in the obesity, on TJ permeability were explored in human intestinal Caco-2 cells.</p> <p>Results</p> <p>The OLETF rats showed higher glucose intolerance than did the LETO rats, which became more marked with the prolonged feeding of the high fat diet. Intestinal permeability in the OLETF rats evaluated by the urinary excretion of intestinal permeability markers (Cr-EDTA and phenolsulfonphthalein) was comparable to that in the LETO rats. Feeding the high fat diet increased intestinal permeability in both the OLETF and LETO rats, and the increases correlated with decreases in TJ proteins (claudin-1, claudin-3, occludin and junctional adhesion molecule-1) expression in the small, but not in the large intestine (cecum or colon). The plasma bile acids concentration was higher in rats fed the high fat diet. Exposure to bile juice and the fat emulsion increased TJ permeability with concomitant reductions in TJ protein expression (claudin-1, claudin-3, and junctional adhesion molecule-1) in the Caco-2 cell monolayers.</p> <p>Conclusion</p> <p>Excessive dietary fat and/or increased levels of luminal bile juice, but not genetic obesity, are responsible for the increase in small intestinal permeability resulting from the suppression of TJ protein expression.</p

Unsupervised Human Activity Recognition through Two-stage Prompting with ChatGPT

Wearable sensor devices, which offer the advantage of recording daily objects used by a person while performing an activity, enable the feasibility of unsupervised Human Activity Recognition (HAR). Unfortunately, previous unsupervised approaches using the usage sequence of objects usually require a proper description of activities manually prepared by humans. Instead, we leverage the knowledge embedded in a Large Language Model (LLM) of ChatGPT. Because the sequence of objects robustly characterizes the activity identity, it is possible that ChatGPT already learned the association between activities and objects from existing contexts. However, previous prompt engineering for ChatGPT exhibits limited generalization ability when dealing with a list of words (i.e., sequence of objects) due to the similar weighting assigned to each word in the list. In this study, we propose a two-stage prompt engineering, which first guides ChatGPT to generate activity descriptions associated with objects while emphasizing important objects for distinguishing similar activities; then outputs activity classes and explanations for enhancing the contexts that are helpful for HAR. To the best of our knowledge, this is the first study that utilizes ChatGPT to recognize activities using objects in an unsupervised manner. We conducted our approach on three datasets and demonstrated the state-of-the-art performance.Comment: 4 page

Mechanisms of Significant Precipitation Hardening in a Medium Carbon Bainitic Steel by Complex Nanocarbides Composed of Nb, Ti and V

Precipitation-hardening behavior of various medium carbon bainitic steels with added elements of Nb, Ti and V was systematically investigated. Complex nanocarbides composed of Nb, Ti and V precipitated after aging in the steel with multiple additions of all the elements, whereas those with added individual elements were simple MC types. The amount of precipitation hardening (ΔHv) after aging at 873 K of the former steel was approximately 90 ΔHv, while those of the latter were less than 40 ΔHv at best. Therefore, significant precipitation hardening took place by multiple element addition. The different amount of precipitation hardening depending on added elements was reasonably understood by considering misfit parameters between carbides and ferrite matrix

Cellular Fragments as Biomaterial for Rapid In Vitro Bone-Like Tissue Synthesis

Current stem cell-based techniques for bone-like tissue synthesis require at least two to three weeks. Therefore, novel techniques to promote rapid 3D bone-like tissue synthesis in vitro are still required. In this study, we explored the concept of using cell nanofragments as a substrate material to promote rapid bone formation in vitro. The methods for cell nanofragment fabrication were ultrasonication (30 s and 3 min), non-ionic detergent (triton 0.1% and 1%), or freeze-dried powder. The results showed that ultrasonication for 3 min allowed the fabrication of homogeneous nanofragments of less than 150 nm in length, which mineralized surprisingly in just one day, faster than the fragments obtained from all other methods. Further optimization of culture conditions indicated that a concentration of 10 mM or 100 mM of beta-glycerophosphate enhanced, whereas fetal bovine serum (FBS) inhibited in a concentration-dependent manner, the mineralization of the cell nanofragments. Finally, a 3D collagen-cell nanofragment-mineral complex mimicking a bone-like structure was generated in just two days by combining the cell nanofragments in collagen gel. In conclusion, sonication for three min could be applied as a novel method to fabricate cell nanofragments of less than 150 nm in length, which can be used as a material for in vitro bone tissue engineering

Rapid bioinspired mineralization using cell membrane nanofragments and alkaline milieu

Bone is a sophisticated organic-inorganic hybrid material, whose formation involves a complex spatio-temporal sequence of events regulated by the cells. A deeper understanding of the mechanisms behind bone mineralization at different size scales, and using a multidisciplinary approach, may uncover novel pathways for the design and fabrication of functional bone tissue in vitro. The objectives of this study were first to investigate the environmental factors that prime initial mineralization using the secondary ossification center as an in vivo model, and then to apply the obtained knowledge for rapid in vitro synthesis of bone-like tissue. First, the direct and robust measurement of pH showed that femur epiphysis is alkaline (pH ≅ 8.5) at the initial mineral stage at post-natal day 6. We showed that the alkaline milieu is decisive not only for alkaline phosphatase activity, which precedes mineral formation at P6, but also for determining initial mineral precipitation and spherical morphology. Next, engineering approaches were used to synthesize bone-like tissue based on alkaline milieu and artificial chondrocyte membrane nanofragments, previously shown to be the nucleation site for mineral formation. Interestingly, mineralization using artificial cell membrane nanofragments was achieved in just 1 day. Finally, ex vivo culture of femur epiphysis in alkaline pH strongly induced chondrocyte burst, which was previously shown to be the origin of chondrocyte membrane nanofragments, and also enhanced mineral formation. Taken together, these findings not only shed more light on the microenvironmental conditions that prime initial bone formation in vivo, but they also show that alkaline milieu can be used as an important factor for enhancing methods for in vitro synthesis of bone tissue.Hara E.S., Okada M., Kuboki T., et al. Rapid bioinspired mineralization using cell membrane nanofragments and alkaline milieu. Journal of Materials Chemistry B, 6, 38, 6153. https://doi.org/10.1039/C8TB01544A

Important roles of odontoblast membrane phospholipids in early dentin mineralization

The objective of this study was to first identify the timing and location of early mineralization of mouse first molar, and subsequently, to characterize the nucleation site for mineral formation in dentin from a materials science viewpoint and evaluate the effect of environmental cues (pH) affecting early dentin formation. Early dentin mineralization in mouse first molars began in the buccal central cusp on post-natal day 0 (P0), and was first hypothesized to involve collagen fibers. However, elemental mapping indicated the co-localization of phospholipids with collagen fibers in the early mineralization area. Co-localization of phosphatidylserine and annexin V, a functional protein that binds to plasma membrane phospholipids, indicated that phospholipids in the pre-dentin matrix were derived from the plasma membrane. A 3-dimensional in vitro biomimetic mineralization assay confirmed that phospholipids from the plasma membrane are critical factors initiating mineralization. Additionally, the direct measurement of the tooth germ pH, indicated it to be alkaline. The alkaline environment markedly enhanced the mineralization of cell membrane phospholipids. These results indicate that cell membrane phospholipids are nucleation sites for mineral formation, and could be important materials for bottom-up approaches aiming for rapid and more complex fabrication of dentin-like structures

Re-Evaluation of Initial Bone Mineralization from an Engineering Perspective

Bone regeneration was one of the earliest fields to develop in the context of tissue regeneration, and currently, repair of small-sized bone defects has reached a high success rate. Future researches are expected to incorporate more advanced techniques toward achieving rapid bone repair and modulation of the regenerated bone quality. For these purposes, it is important to have a more integrative understanding of the mechanisms of bone formation and maturation from multiple perspectives and to incorporate these new concepts into the development and designing of novel materials and techniques for bone regeneration. This review focuses on the analysis of the earliest stages of bone tissue development from the biology, material science, and engineering perspectives for a more integrative understanding of bone formation and maturation, and for the development of novel biology-based engineering approaches for tissue synthesis in vitro. More specifically, the authors describe the systematic methodology that allowed the understanding of the different nucleation sites in intramembranous and endochondral ossification, the space-making process for mineral formation and growth, as well as the process of apatite crystal cluster growth in vivo in the presence of suppressing biomolecules. A detailed understanding of the developmental process of bone tissue leads to the acquisition of useful information for the bone tissue fabrication. This review summarizes the study of the calcification process of the calvaria and epiphyses from an engineering perspective and provides useful information for the realization of bone tissue biofabrication. Here, we describe the new mechanism of space formation for mineralization such as rupture of chondrocytes and disruption of cell-cell adhesion. We also describe the roles of nucleation site such as cell membrane nanofragments and matrix vesicles.Hara E.S., Okada M., Nagaoka N., et al. Re-Evaluation of Initial Bone Mineralization from an Engineering Perspective. Tissue Engineering - Part B: Reviews, 28, 1, 246. https://doi.org/10.1089/ten.teb.2020.0352

Titanium as an Instant Adhesive for Biological Soft Tissue

A variety of polymer‐ and ceramic‐based soft‐tissue adhesives have been developed as alternatives to surgical sutures, yet several disadvantages regarding the mechanical properties, biocompatibility, and handling hinder their further application particularly when applied for immobilization of implantable devices. Here, it is reported that a biocompatible and tough metal, titanium (Ti), shows instant and remarkable adhesion properties after acid treatment, demonstrated by ex vivo shear adhesion tests with mouse dermal tissues. Importantly, in vivo experiments demonstrate that the acid‐treated Ti can easily and stably immobilize a device implanted in the mouse subcutaneous tissue. Collectively, the acid‐treated Ti is shown as a solid‐state instant adhesive material for biological soft tissues, which can have diverse applications including immobilization of body‐implantable devices

Micro-Architectural Investigation of Teleost Fish Rib Inducing Pliant Mechanical Property

Despite the fact that various reports have been discussing bone tissue regeneration, precise bone tissue manipulation, such as controlling the physical properties of the regenerated bone tissue, still remains a big challenge. Here, we focused on the teleost fish ribs showing flexible and tough mechanical properties to obtain a deeper insight into the structural and functional features of bone tissue from different species, which would be valuable for the superior design of bone-mimicking materials. Herein, we examined their compositions, microstructure, histology, and mechanical properties. The first rib of Carassius langsdorfii showed a higher Young's modulus with a small region of chondrocyte clusters compared with other smaller ribs. In addition, highly oriented collagen fibers and osteocytes were observed in the first rib, indicating that the longest first rib would be more mature. Moreover, the layer-by-layer structure of the oriented bone collagen was observed in each rib. These microarchitectural and compositional findings of fish rib bone would give one the useful idea to reproduce such a highly flexible rib bone-like material