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To evaluate the effect of local parathyroid hormone (PTH) administration on rotator cuff tendon‐to‐bone healing in a rat model compared with systemic PTH injection and untreated controls. PTH‐alginate scaffold was prepared and sustained release of PTH was confirmed. Bilateral supraspinatus tendon repairs were performed in 39 rats (group 1, supraspinatus repair only; group 2, supraspinatus repair with systemic PTH injection; group 3, supraspinatus repair with local PTH administration via an absorbable scaffold; n = 13 each). Biomechanical (cross‐sectional area, mode of failure, load to failure, and ultimate stress: right side) and histological analyses (hematoxylin and eosin stain, Masson's Trichrome stain Picrosirius red stain, Immunohistochemistry for BMP2, PTH1R, ColI, and ColIII: Left side) were performed to evaluate tendon‐to‐bone healing quality at 8 weeks after repair, and blood test (osteocalcin and procollagen type I N‐terminal pro‐peptide [PINP] levels) was performed in all rats. There was no intergroup difference in the healing failure rate (p = 0.910) or failure mode (p = 0.585). Biomechanically, subjects in groups 2 and 3 exhibited significantly larger cross‐sectional areas and higher ultimate failure loads and ultimate stress than those in group 1 (all p < 0.05); however, no differences were noted between groups 2 and 3 (all p > 0.05). Histologically, groups 2 and 3 exhibited more organized tendon‐to‐bone interface structures with higher density, parallel orientation, and collagen fiber continuity than group 1 (all p < 0.05 except collagen fiber continuity in group 1 vs. 2); however, no differences in histological parameters between groups 2 and 3 (all p > 0.05). The protein levels of bone morphogenic protein 2, PTH 1 receptor, and collagen I and III and the serum level of PINP were increased in groups 2 and 3 versus group 1 (all p < 0.05) without showing differences between groups 2 and 3 (all p > 0.05). Local PTH administration using an absorbable scaffold improved the biomechanical and histological outcomes of rotator cuff tendon‐to‐bone healing comparable with systemic PTH injection at 8 weeks after repair in a rat model. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:82–91, 2020 [ABSTRACT FROM AUTHOR]

Background Fatty infiltration in skeletal muscle is directly linked to loss of muscle strength and is associated with various adverse physical outcomes such as muscle atrophy, inflammation, insulin resistance, mobility impairments, and even mortality in the elderly. Aging, mechanical unloading, muscle injury, and hormonal imbalance are main causes of muscle fat accumulation, and the fat cells are derived from muscle stem cells via adipogenic differentiation. However, the pathogenesis and molecular mechanisms of fatty infiltration in muscles are still not fully defined. Fatty acid-binding protein 4 (FABP4) is a carrier protein for fatty acids and is involved in fatty acid uptake, transport, and lipid metabolism. Rotator cuff tear (RCT) usually occurs in the elderly and is closely related with fatty infiltration in injured muscle. To investigate potential mechanisms for fatty infiltration other than adipogenic differentiation of muscle stem cells, we examined the role of FABP4 in muscle fatty infiltration in an RCT mouse model. Methods In the RCT model, we evaluated the expression of FABP4 by qRT-PCR, western blotting, and immunohistochemical analyses. Histological changes such as inflammation and fat accumulation in the injured muscles were examined immunohistochemically. To evaluate whether hypoxia induces FABP4 expression, the levels of FABP4 mRNA and protein in C3H10T1/2 cells after hypoxia were examined. Using a transient transfection assay in 293T cells, we assessed the promoter activity of FABP4 by hypoxia-inducible factors (HIFs). Additionally, we evaluated the reduction in FABP4 expression and fat accumulation using specific inhibitors for HIF1 and FABP4, respectively. Results FABP4 expression was significantly increased after RCT in mice, and its expression was localized in the intramuscular fatty region. Rotator cuff tear-induced FABP4 expression was up-regulated by hypoxia. HIF1α, which is activated by hypoxia, augmented the promoter activity of FABP4, together with HIF1β. Hypoxia-induced FABP4 expression was significantly decreased by HIF1 inhibitor treatment. Furthermore, in RCT model mice, fat accumulation was remarkably reduced by FABP4 inhibitor treatment. Conclusions This study shows that RCT induces FABP4 expression, leading to fat accumulation in injured muscle. FABP4 transcription is regulated by the direct binding of HIF1 to the FABP4 promoter in the hypoxic condition induced by RCT. Fat accumulation in injured muscle was reduced by the inhibition of FABP4. Ultimately, in the RCT model, we identified a novel mechanism for fatty infiltration by FABP4, which differs from adipogenic differentiation of muscle stem cells, and we found that fatty infiltration might be regulated by inhibition of HIF1 or FABP4. [ABSTRACT FROM AUTHOR]

We present a new semi-insulating carbon-doped GaN/undoped GaN multi-layered buffer structure for AlGaN/GaN heterojunction field effect transistors, which drastically suppresses current collapse in GaN MISHFET with improving the on-current performance of the device but without degrading the breakdown characteristic. It is believed that spatial compensation between the multi-layered GaN layers not only makes the multi-layered buffer layer very highly resistive, but also prevents the electrons from the 2DEG channel from being captured into deep traps in the buffer layer, which maintains high-high breakdown characteristic and leads to great suppression of current collapse in AlGaN/GaN-based transistors, respectively. [ABSTRACT FROM AUTHOR]

Objective: The hypothalamus is the brain center that controls the energy balance. Anorexigenic proopiomelanocortin (POMC) neurons and orexigenic AgRP neurons in the arcuate nucleus of the hypothalamus plays critical roles in energy balance regulation. FoxO1 is a transcription factor regulated by insulin signaling that is deacetylated by Sirt1, a nicotinamide adenine dinucleotide- (NAD(+) -) dependent deacetylase. Overexpression of insulin-resistant constitutively-nuclear FoxO1 (CN-FoxO1) in POMC neurons leads to obesity, whereas Sirt1 overexpression in POMC neurons leads to leanness. Whether overexpression of Sirt1 in POMC neurons could rescue the obesity caused by insulin-resistant CN-FoxO1 was tested here.Methods: POMC neuron-specific CN-FoxO1/Sirt1 double-KI (DKI) mice were analyzed.Results: The obese phenotype of CN-FoxO1 KI mice was rescued in male DKI mice. Reduced O2 consumption, increased adiposity, and fewer POMC neurons observed in CN-FoxO1 mice were rescued in male DKI mice without affecting food intake and locomotor activity. Sirt1 overexpression decreased FoxO1 acetylation and protein levels without affecting its nuclear localization in mouse embryonic fibroblasts and hypothalamic N41 cells.Conclusions: Sirt1 rescues the obesity induced by insulin-resistant CN-FoxO1 in POMC neurons of male mice by decreasing FoxO1 protein through deacetylation. Sirt1 ameliorates obesity caused by a genetic model of central insulin resistance. [ABSTRACT FROM AUTHOR]

The flowers of Carthamus tinctorius L. (Compositae) have been widely used for enhancing blood circulation and postmenopausal disorder in women. In the present study, the potential protective effects of C. tinctorius flower extract (CFE) against reactive oxygen species (ROS) induced osteoblast dysfunction were investigated using osteoblastic MC3T3-E1 cells. The osteoblast function was assessed by measuring alkaline phosphatase activity, collagen content, calcium deposition, and RANKL production, and the oxidative status was assessed by measuring intracellular lipid peroxidation, and protein oxidation in osteoblastic MC3T3-E1 cells. A significant reduction in the alkaline phosphatase activity, collagen, and calcium deposition and an increase in the production of receptor activator of nuclear factor-kB ligand (RANKL) were observed after 0.3 mM H2O2 addition. The H2O2-induced alterations were prevented by pre-incubating the osteoblasts with 2-10 μg/ml CFE for 48 h. When the oxidative stress was induced by H2O2, the increased production of protein carbonyl and malondialdehyde was also reduced at the same CFE concentration. These results demonstrate that C. tinctorius flower can act as a biological antioxidant in a cell culture experimental model and protect osteoblasts from oxidative stress-induced toxicity. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The rhizome of Atractylodes japonica Koidz. has been used traditionally for the treatment of water retention in the body and is known to have estrogen-like activity. In the present study, the protective effects of A. japonica root extract on the response of osteoblasts to oxidative stress were evaluated. Osteoblastic MC3T3-E1 cells were incubated with hydrogen peroxide and/or A. japonica root extract, and markers of osteoblast function and oxidative damage were examined. A. japonica root extract significantly ( p < 0.05) increased cell survival, alkaline phosphatase activity, collagen and calcium deposition and decreased the production of receptor activator of nuclear factor-kB ligand (RANKL), protein carbonyl and malondialdehyde of osteoblastic MC3T3-E1 cells in the presence of hydrogen peroxide. These results demonstrate that A. japonica root can protect the cells from oxidative stress-induced toxicity and may have positive effects on skeletal structure. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In article number 1800118, Emmanuelle Deleporte, Kyunghwan Oh, and co‐workers combine 2D crystallites perovskite ((C5H5C2H4NH3)2PbI4) with a fiber ring laser to confirm its novel nonlinear optic functionality by generating an ultrafast laser in both transform‐limited soliton and dissipative soliton formats at the spectral range covering entire C‐ and L‐bands. It shows the shortest pulse width, the highest repetition rate, the most stable pulse generation, and the highest slope efficiency compared with prior 3D perovskite‐based pulse lasers. [ABSTRACT FROM AUTHOR]

Two‐dimensional hybrid organic–inorganic perovskites have recently attracted attention in various optoelectronic applications. A novel thin film of 2D perovskite (C6H5C2H4NH3)2PbI4 crystallites is synthesized and its nonlinear optical properties are experimentally investigated within the optical gain of an Erbium‐doped fiber. Utilizing its unique nonlinear optical response, efficient mode‐locking of an all‐fiber Erbium laser is demonstrated at the anomalous dispersion regime in both the C‐ and L‐bands stably generating femtosecond pulse trains, where the thin film of 2D perovskite crystallites function as an in‐line saturable absorber. At this anomalous dispersion regime, self‐started femtosecond pulses are generated whose center wavelength are tuned from 1565.9 nm in C‐band and 1604 nm in L‐band by adjusting the optical gain. Furthermore, by managing the chromatic dispersion of the total fiber laser cavity to reach the normal dispersion regime, a stable dissipative soliton is successfully generated in the C‐band with the spectral bandwidth of 15 nm and pulse duration of 3.2 ps. Detailed material properties of the thin film of 2D perovskite crystallites, their characterization, and fiber laser mode‐locking performance is reported. A two‐dimensional crystallites perovskite ((C6H5C2H4NH3)2PbI4) is combined with a fiber laser to confirm its nonlinear optic functionality by generating an ultrafast laser in both transform‐limited soliton and dissipative soliton formats in the entire C‐ and L‐bands. It shows the shortest pulse width, the highest repetition rate, the most stable pulse generation, and the highest slope efficiency compared with 3D perovskite‐based pulse lasers. [ABSTRACT FROM AUTHOR]