Macro- to Microscale Strain Transfer in Fibrous Tissues is Heterogeneous and Tissue-Specific

AbstractMechanical deformation applied at the joint or tissue level is transmitted through the macroscale extracellular matrix to the microscale local matrix, where it is transduced to cells within these tissues and modulates tissue growth, maintenance, and repair. The objective of this study was to investigate how applied tissue strain is transferred through the local matrix to the cell and nucleus in meniscus, tendon, and the annulus fibrosus, as well as in stem cell-seeded scaffolds engineered to reproduce the organized microstructure of these native tissues. To carry out this study, we developed a custom confocal microscope-mounted tensile testing device and simultaneously monitored strain across multiple length scales. Results showed that mean strain was heterogeneous and significantly attenuated, but coordinated, at the local matrix level in native tissues (35–70% strain attenuation). Conversely, freshly seeded scaffolds exhibited very direct and uniform strain transfer from the tissue to the local matrix level (15–25% strain attenuation). In addition, strain transfer from local matrix to cells and nuclei was dependent on fiber orientation and tissue type. Histological analysis suggested that different domains exist within these fibrous tissues, with most of the tissue being fibrous, characterized by an aligned collagen structure and elongated cells, and other regions being proteoglycan (PG)-rich, characterized by a dense accumulation of PGs and rounder cells. In meniscus, the observed heterogeneity in strain transfer correlated strongly with cellular morphology, where rounder cells located in PG-rich microdomains were shielded from deformation, while elongated cells in fibrous microdomains deformed readily. Collectively, these findings suggest that different tissues utilize distinct strain-attenuating mechanisms according to their unique structure and cellular phenotype, and these differences likely alter the local biologic response of such tissues and constructs in response to mechanical perturbation

G-protein-coupled receptor 81 promotes a malignant phenotype in breast cancer through angiogenic factor secretion

G-protein-coupled receptor 81 (GPR81) functions as a receptor for lactate and plays an important role in the regulation of anti-lipolytic effects in adipocytes. However, to data, a role for GPR81 in the tumor microenvironment has not been clearly defined. Here, GPR81 expression in breast cancer patients and several breast cancer cell lines was significantly increased compared with normal mammary tissues and cells. GPR81 knockdown resulted in impaired breast cancer growth and led to apoptosis both in vitro and in vivo. Furthermore, the inhibition of GPR81 signaling suppressed angiogenesis through a phosphoinositide 3-OH kinase (PI3K)/Akt-cAMP response element binding protein (CREB) pathway, which led to decreased production of the pro-angiogenic mediator amphiregulin (AREG). Overall, these findings identify GPR81 as a tumor-promoting receptor in breast cancer progression and suggest a novel mechanism that regulates GPR81-dependent activation of the PI3K/Akt signaling axis in tumor microenvironment.open

Effects of different creep feed types on pre-weaning and post-weaning performance and gut development

Objective This experiment was carried out to determine the effects of different creep feed types on suckling performance and further adjustments to solid feed after weaning. Methods A total of 24 multiparous sows and their litters were allotted to one of three treatment groups: i) provided highly digestible creep feed (Creep), ii) provided a pig weaning diet (Weaner), and iii) provided sow feed (Sow) as creep feed until weaning. After weaning, a total of 96 piglets were selected for evaluation of post-weaning performance. Results For pre-weaning performance, the Creep treatment led to a significantly higher feed intake from 14 to 28 d (p<0.05) and higher body weight gain from 21 to 28 d than piglets that were provided other diets. However, after weaning, the Weaner treatment yielded a significantly higher feed intake and average daily gain than other treatments from 0 to 14 d after weaning (p<0.05); Creep treatment tended to generate lower villus heights in the duodenum than the other treatments (p = 0.07). Conclusion Highly digestible creep feed improved pre-weaning performance, but feed familiarity and grain-based creep feed improved post-weaning performance

pH-responsive high-density lipoprotein-like nanoparticles to release paclitaxel at acidic pH in cancer chemotherapy

Jae-Yoon Shin,1,* Yoosoo Yang,1,* Paul Heo,1 Ji-Chun Lee,1 ByoungJae Kong,1 Jae Youl Cho,1 Keejung Yoon,1 Cheol-Su Shin,2 Jin-Ho Seo,3 Sung-Gun Kim,4 Dae-Hyuk Kweon11Department of Genetic Engineering, College of Biotechnology and Bioengineering, and Center for Human Interface Nano Technology, Sungkyunkwan University, 2APTech Research Center, Suwon, 3Department of Agricultural Biotechnology, Seoul National University, Seoul, 4Department of Biomedical Science, Youngdong University, Chungbuk, South Korea*These authors contributed equally to this workBackground: Nanoparticles undergoing physicochemical changes to release enclosed drugs at acidic pH conditions are promising vehicles for antitumor drug delivery. Among the various drug carriers, high-density lipoprotein (HDL)-like nanoparticles have been shown to be beneficial for cancer chemotherapy, but have not yet been designed to be pH-responsive.Methods and results: In this study, we developed a pH-responsive HDL-like nanoparticle that selectively releases paclitaxel, a model antitumor drug, at acidic pH. While the well known HDL-like nanoparticle containing phospholipids, phosphatidylcholine, and apolipoprotein A-I, as well as paclitaxel (PTX-PL-NP) was structurally robust at a wide range of pH values (3.8&amp;ndash;10.0), the paclitaxel nanoparticle that only contained paclitaxel and apoA-I selectively released paclitaxel into the medium at low pH. The paclitaxel nanoparticle was stable at physiological and basic pH values, and over a wide range of temperatures, which is a required feature for efficient cancer chemotherapy. The homogeneous assembly enabled high paclitaxel loading per nanoparticle, which was 62.2% (w/w). The molar ratio of apolipoprotein A-I and paclitaxel was 1:55, suggesting that a single nanoparticle contained approximately 110 paclitaxel particles in a spherical structure with a 9.2 nm diameter. Among the several reconstitution methods applied, simple dilution following sonication enhanced the reconstitution yield of soluble paclitaxel nanoparticles, which was 0.66. As a result of the pH responsiveness, the anticancer effect of paclitaxel nanoparticles was much more potent than free paclitaxel or PTX-PL-NP.Conclusion: The anticancer efficacy of both paclitaxel nanoparticles and PTX-PL-NP was dependent on the expression of scavenger receptor class B type I, while the killing efficacy of free paclitaxel was independent of this receptor. We speculate that the pH responsiveness of paclitaxel nanoparticles enabled efficient endosomal escape of paclitaxel before lysosomal break down. This is the first report on pH-responsive nanoparticles that do not contain any synthetic polymer.Keywords: pH responsiveness, nanoparticle, apolipoprotein A-I, paclitaxe

Mechanotransductive feedback control of endothelial cell motility and vascular morphogenesis

Vascular morphogenesis requires persistent endothelial cell motility that is responsive to diverse and dynamic mechanical stimuli. Here, we interrogated the mechanotransductive feedback dynamics that govern endothelial cell motility and vascular morphogenesis. We show that the transcriptional regulators, YAP and TAZ, are activated by mechanical cues to transcriptionally limit cytoskeletal and focal adhesion maturation, forming a conserved mechanotransductive feedback loop that mediates human endothelial cell motility in vitro and zebrafish intersegmental vessel (ISV) morphogenesis in vivo. This feedback loop closes in 4 hours, achieving cytoskeletal equilibrium in 8 hours. Feedback loop inhibition arrested endothelial cell migration in vitro and ISV morphogenesis in vivo. Inhibitor washout at 3 hrs, prior to feedback loop closure, restored vessel growth, but washout at 8 hours, longer than the feedback timescale, did not, establishing lower and upper bounds for feedback kinetics in vivo. Mechanistically, YAP and TAZ induced transcriptional suppression of myosin II activity to maintain dynamic cytoskeletal equilibria. Together, these data establish the mechanoresponsive dynamics of a transcriptional feedback loop necessary for persistent endothelial cell migration and vascular morphogenesis

Overcoming the electroluminescence efficiency limitations of perovskite light-emitting diodes.

Organic-inorganic hybrid perovskites are emerging low-cost emitters with very high color purity, but their low luminescent efficiency is a critical drawback. We boosted the current efficiency (CE) of perovskite light-emitting diodes with a simple bilayer structure to 42.9 candela per ampere, similar to the CE of phosphorescent organic light-emitting diodes, with two modifications: We prevented the formation of metallic lead (Pb) atoms that cause strong exciton quenching through a small increase in methylammonium bromide (MABr) molar proportion, and we spatially confined the exciton in uniform MAPbBr3 nanograins (average diameter = 99.7 nanometers) formed by a nanocrystal pinning process and concomitant reduction of exciton diffusion length to 67 nanometers. These changes caused substantial increases in steady-state photoluminescence intensity and efficiency of MAPbBr3 nanograin layers.This work was partially supported by Samsung Research Funding Center of Samsung Electronics under Project Number SRFC-MA-1402-07. A.S. was partially supported by the Engineering and Physical Sciences Research Council (UK).This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by the American Association for the Advancement of Science

Reversal of Trimethyltin-Induced Learning and Memory Deficits by 3,5-Dicaffeoylquinic Acid

The antiamnesic effect of 3,5-dicaffeoylquinic acid (3,5-diCQA) as the main phenolic compound in Artemisia argyi H. extract on cognitive dysfunction induced by trimethyltin (TMT) (7.1 μg/kg of body weight; intraperitoneal injection) was investigated in order to assess its ameliorating function in mice. In several behavioral tests, namely, the Y-maze, passive avoidance, and Morris water maze (MWM) test, 3,5-diCQA significantly ameliorated learning and memory deficits. After the behavioral tests, brain tissues from the mice were analyzed to characterize the basis of the neuroprotective effect. Acetylcholine (ACh) levels increased, whereas the activity of acetylcholinesterase (AChE) decreased upon administration of 3,5-diCQA. In addition, 3,5-diCQA effectively protected against an increase in malondialdehyde (MDA) content, an increase in the oxidized glutathione (GSH) ratio, and a decline of total superoxide dismutase (SOD) level. 3,5-diCQA may prevent neuronal apoptosis through the protection of mitochondrial activities and the repression of apoptotic signaling molecules such as p-Akt, BAX, and p-tau (Ser 404)

Highly controllable transparent and conducting thin films using layer-by-layer assembly of oppositely charged reduced graphene oxides

A new approach for the fabrication of reduced graphene oxide (rGO) multilayers which can be used for transparent and conducting thin films was developed. This was achieved by using layer-by-layer (LbL) assembly of positively and negatively charged rGO sheets, which could provide highly controllable thin films in terms of thickness, transmittance, and sheet resistance. In particular, the thickness of the multilayer thin films of rGO was able to be controlled precisely in the subnanometre scale by similar to 0.46 nm via simply varying the number of stacking layers. Therefore, this method enabled an excellent control of the rGO multilayers over the optical and electrical properties, which are related to the thickness. Furthermore, we demonstrated the application of the rGO multilayers for an OLED device.close585

Anti-inflammatory effect of supercritical extract and its constituents from Ishige okamurae

The anti-inflammatory properties of the supercritical fluid extract of Ishige okamurae (SFEIO) on lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages. The lipid profile of the SFEIO, reviled the presence of palmitic acid (220.2 mg/g), linoleic acid (168.0 mg/g), and oleic acid (123.0 mg/g). SFEIO was found to exert it’s anti-inflammatory effects through inhibiting nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 production in LPS-stimulated RAW 264.7 cells, without inducing cytotoxicity. SFEIO did not effect on the LPS-induced p38 kinase phosphorylation, whereas it attenuated the extracellular-related signaling kinase (ERK) and c-Jun N-terminal kinase (JNK) phosphorylation. Furthermore, SFEIO inhibited the LPS-induced IκB-α degradation and p50 NF-κB activation. These results suggest that SFEIO exerts its anti-inflammatory effects in LPS-activated RAW 264.7 cells by down-regulating the activation of ERK, JNK, and NF-κB