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Li-rich layered oxides (LRLO) exhibit significant potential for use in all-solid-state lithium batteries (ASSLBs) owing to their high capacities and wide range of operating voltages. However, the practical application of LRLO in ASSLBs is hindered by the severe failure of carrier transport at the solid--solid interface, which subsequently limits the electrochemical activity of these batteries. Here, the spatially asynchronous activation mechanism of the LRLO in ASSLBs is presented. A spectroscopic study extending from the surface into the bulk interior of LRLO indicates that the activation kinetics of anionic oxygen prefers hysteretic delivery over uniform delivery and fast transition metals (TMs) activation. This spatial hetero activation is dominated by the failure of carrier transport at the interface, which is induced by microstructural defects in the composite cathode. This study is expected to facilitate the microstructural design of high-performance LRLO-based ASSLBs. [ABSTRACT FROM AUTHOR]

Background: X‐linked hypophosphatemic rickets (XLH) is a heterogeneous genetic phosphate wasting disorder that occupies the majority of inheritable hypophosphatemic rickets (HR). XLH is caused by loss‐of‐function mutations in the phosphate‐regulating endopeptidase gene (PHEX) located on the X chromosome. Method: In this study, we performed whole‐exome sequencing (WES) on the proband to identify the causative gene. The mutations were analyzed by predictive online software, such as PolyPhen‐2. Plasmids containing the wild‐type (WT) and mutant cDNA of the candidate gene were transfected into HEK293, then, the expression, cellular localization, and glycosylation state of the candidate proteins were detected by western blot, immunostaining, and endoglycosidase H digestion. The expression and concentration of related factor were measured by RT‐PCR and ELISA. Results: We identified a novel missense mutation c.2179T>C in the PHEX that results in the substitution of p.Phe727Leu (F727L). This mutation was predicted to be disease‐causing by all four predictive online software. In vitro studies demonstrated that the F727L substitution hindered the intracellular trafficking of the mutant PHEX, with ~59% of mutant PHEX protein retained in the endoplasmic reticulum (ER) and only ~16% of the mutant protein localized on the cell surface. Endoglycosidase H digestion assay showed that the mutant F727L PHEX protein was not fully glycosylated. The concentration of intact FGF23 in hFOB1.19 cell culture medium collected from the mutant PHEX group was the highest (62.9 pg/ml) compared to the WT group (32.1 pg/ml) and control group (23.5 pg/ml). Conclusion: Our results confirmed that the mutant PHEX protein was lowly glycosylated and retarded within the ER, the intact FGF23 level in cell culture media caused by the mutant PHEX protein was significantly elevated compared to that of the WT group, which may explain why the single base mutation in the PHEX led to XLH syndrome in this family. [ABSTRACT FROM AUTHOR]

We demonstrate the use of two different wavelength ranges of excitation light as inputs to remotely trigger the responses of the self-assembled DNA devices (D-OR). As an important feature of this device, the dependence of the readout fluorescent signals on the two external inputs, UVexcitation for 1 min and/or near infrared irradiation (NIR) at 800 nmfs laser pulses, can mimic function of signal communication in OR logic gates. Their operations could be reset easily to its initial state. Furthermore, these DNA devices exhibit efficient cellular uptake, low cytotoxicity, and high bio-stability in different cell lines. They are considered as the first example of a photoresponsive DNA logic gate system, as well as a biocompatible, multi-wavelength excited system in response to UV and NIR. This is an important step to explore the concept of photoresponsive DNA-based systems as versatile tools in DNA computing, display devices, optical communication, and biology. [ABSTRACT FROM AUTHOR]

Chondrocytes phenotype/markers were expressed in clinical samples of tendinopathy and calcifying tendinopathy. This study examined the spatial-temporal expression of chondro-osteogenic Bone Morphogenetic Proteins (BMPs), which might contribute to ectopic chondro-osteogenesis and failed healing process in tendinopathy. Collagenase was injected into patellar tendon of rats to induce ossified failed tendon healing. At week 2, 4, 8, 12, and 16, the patella tendon was harvested for immunohistochemical staining and analysis of BMP-2/4/7. BMP-4/7 showed similar expression patterns, which was different from BMP-2. The expression of BMP-2 in the tendon matrix increased at week 2 and was reduced to nearly undetectable level afterwards except at the chondro-ossification sites. However, the expression of BMP-4/7 in the healing tendon fibroblast-like cells and matrix increased at week 2, reduced at week 4 and 8 and increased again at week 12 and 16, consistent with transient healing at week 8 in this animal model. There was increasing strong expression of BMP-4/7 in the chondrocyte-like cells in the un-ossified and ossified areas from week 8-16. BMP-4/7, besides BMP-2, might also contribute to ectopic chondro-osteogenesis and failed healing in tendon injuries. BMP-4/7, but not BMP-2, might be involved in regulating late events in ossified failed tendon healing. © 2010 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:816-821 [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effect of repetitive tensile loading on the expression of BMP-2 and the effect of BMP-2 on the osteogenic differentiation of tendon-derived stem cells (TDSCs) in vitro. Repetitive stretching was applied to TDSCs isolated from rat patellar tendon at 0%, 4%, and 8%, 0.5 Hz. The expression of BMP-2 was detected by Western blotting and qPCR. To study the osteogenic effects of BMP-2 on TDSCs, BMP-2 was added to the TDSC monolayer for the detection of ALP activity and calcium nodule formation in a separate experiment. TDSCs adhered, proliferated, and aligned along the direction of externally applied tensile force while they were randomly oriented in the control group. Western blotting showed increased expression of BMP-2 in 4% and 8% stretching groups but not in the control group. Up-regulation of BMP-2 mRNA was also observed in the 4% stretching group. BMP-2 increased the osteogenic differentiation of TDSCs as indicated by higher ALP cytochemical staining, ALP activity, and calcium nodule formation. Repetitive tensile loading increased the expression of BMP-2 and addition of BMP-2 enhanced osteogenic differentiation of TDSCs. Activation of BMP-2 expression in TDSCs during tendon overuse might provide a possible explanation of ectopic calcification in calcifying tendinopathy. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:390-396, 2011 [ABSTRACT FROM AUTHOR]

Melatonin is a highly effective treatment in different animal models of excitotoxicity or ischemia/reperfusion injury. Due to a lack of patentability, commercial sponsors are not interested in funding clinical evaluations of melatonin. Investigators may initiate small-scale clinical evaluation, and intravenous (i.v.) administration is appropriate in acute stroke patients. Institutional Review Boards may require proper preclinical evaluation of the preparation. In this pharmacokinetic and safety study, melatonin in propylene glycol was evaluated in adult male Sprague–Dawley rats. Following a single i.v. injection at 5 or 15 mg/kg, plasma concentrations of melatonin increased to 39 and 199 million pg/mL at 2 min and 128 000 and 772 000 pg/mL at 120 min. Within 60 min of injection, the blood pressure, heart rate and body temperature remained unaffected. Melatonin at 5 mg/kg did not influence the complete blood counts at 60 min, but melatonin at 15 mg/kg had some effects on the differential white cell and platelet counts. Melatonin at 5 or 15 mg/kg slightly elevated some liver enzymes at 60 min of injection, and melatonin at higher dose also elevated plasma creatinine and lactate dehydrogenase levels. At 24 hr after completion of six daily injections of melatonin, there was a 5.5% reduction in body weight. Gross postmortem examination and histological examination of the brain, kidney, liver and spleen did not reveal any evidence of toxicity. In conclusion, melatonin in propylene glycol markedly elevates plasma levels of melatonin with no serious toxicity. This preparation should be further evaluated in human patients. [ABSTRACT FROM AUTHOR]

Men have a higher incidence of coronary heart disease than women at similar age until the age of 50. This finding has led to the hypothesis that testosterone may be a risk factor for coronary heart disease. However, the vascular actions of testosterone remain to be fully elucidated. The aim of this study was to investigate the relationship between testosterone and vascular reactivity, and the mechanism underlying this action. Changes in isometric tension were recorded in isolated rings of porcine coronary arteries. Rings, with disrupted endothelium, were incubated with testosterone in the absence or presence of various pharmacological inhibitors. Dose-response of the contraction agent, U46619 (a stable thromboxane A2 analogue), was then determined. Testosterone significantly enhanced contraction to U46619 in porcine coronary arteries. This effect of testosterone increased with increasing concentration, and was not affected by KT 5823 (a protein kinase G inhibitor). On the other hand, enhancement of U46619-induced contraction in porcine coronary arteries by testosterone was abolished by SQ 22536 (an adenylate cyclase inhibitor) or KT 5720 (a protein kinase A inhibitor). Our result suggested that the effect of testosterone on enhancement of contraction involved the cAMP pathway but not the cGMP pathway. [ABSTRACT FROM AUTHOR]