Summary Objective Disruptions of extracellular matrix (ECM) homeostasis are key events in the pathogenesis of osteoarthritis (OA). MicroRNA-140 (miRNA-140) is expressed specifically in cartilage and ...regulates ECM-degrading enzymes. Our objective in this study was to determine if intra-articular injection of miRNA-140 can attenuate OA progression in rats. Design miRNA-140 levels in human normal and OA cartilage derived chondrocytes and synovial fluid were assessed by polymerase chain reaction (PCR). After primary human chondrocytes were transfected with miRNA-140 mimic or inhibitor, PCR and western blotting were performed to quantify Collagen II, MMP-13, and ADAMTS-5 expression. An OA model was induced surgically in rats, and subsequently treated with one single intra-articular injection of miRNA-140 agomir. At 4, 8, and 12 weeks after surgery, OA progression were evaluated macroscopically, histologically, and immunohistochemically in these rats. Results miRNA-140 levels were significantly reduced in human OA cartilage derived chondrocytes and synovial fluid compared with normal chondrocytes and synovial fluid. Overexpressing miRNA-140 in primary human chondrocytes promoted Collagen II expression and inhibited MMP-13 and ADAMTS-5 expression. miRNA-140 levels in rat cartilage were significantly higher in the miRNA-140 agomir group than in the control group. Moreover, behavioural scores, chondrocyte numbers, cartilage thickness and Collagen II expression levels in cartilage were significantly higher, while pathological scores and MMP-13 and ADAMTS-5 expression levels were significantly lower in the miRNA-140 agomir group than in the control group. Conclusion Intra-articular injection of miRNA-140 can alleviate OA progression by modulating ECM homeostasis in rats, and may have potential as a new therapy for OA.
A wide variety of industrial applications require materials with high strength and ductility. Unfortunately, the strategies for increasing material strength, such as processing to create line defects ...(dislocations), tend to decrease ductility. We developed a strategy to circumvent this in inexpensive, medium manganese steel. Cold rolling followed by low-temperature tempering developed steel with metastable austenite grains embedded in a highly dislocated martensite matrix. This deformed and partitioned (D and P) process produced dislocation hardening but retained high ductility, both through the glide of intensive mobile dislocations and by allowing us to control martensitic transformation. The D and P strategy should apply to any other alloy with deformation-induced martensitic transformation and provides a pathway for the development of high-strength, high-ductility materials.
A new multi-layer irrotational Boussinesq-type model is proposed for both linear and nonlinear surface water waves over mildly sloping seabeds. The model is formulated in terms of computational ...horizontal and vertical velocity components within each layer and satisfies exact kinematic and dynamic free-surface conditions as well as kinematic seabed conditions. Using a Stokes-type expansion, a theoretical analysis of the new multi-layer model is carried out to examine both linear and nonlinear properties, including wave celerity, velocity profiles, shoaling amplitude, second- and third-order transfer functions and amplitude dispersion. The dispersive coefficients in the governing equations are determined by optimizing the linear celerity or linear velocity profiles. For example, the four-layer model shows extremely high accuracy and is applicable up to
$kh=667$
–800 (where
$k$
is the wavenumber and
$h$
is a typical water depth) with a 1 % error in wave phase celerity, and up to
$kh=352$
–423 with a 1 % error in the linear velocity components. The super- and subharmonic transfer functions are extremely accurate up to
$kh=300$
(1 % error), the third-order harmonics and amplitude dispersion are accurate up to
$kh=477$
(1 % error), and the shoaling property is optimized to cover the range of
$0<kh<300$
, which presents a 0.06 % tolerance error in shoaling amplitude. The high-accuracy nature of the model increases its suitability for simulating random wave propagation from extremely deep to shallow waters over mildly sloping topographies. The model is implemented numerically on a non-staggered grid via a composite fourth-order Adams–Bashforth–Moulton time integration. The numerical results show good agreement with both the analytical solutions and experimental data.
Multi-protein complexes called inflammasomes have recently been identified and shown to contribute to cell death in tissue injury. Intravenous immunoglobulin (IVIg) is an FDA-approved therapeutic ...modality used for various inflammatory diseases. The objective of this study is to investigate dynamic responses of the NLRP1 and NLRP3 inflammasomes in stroke and to determine whether the NLRP1 and NLRP3 inflammasomes can be targeted with IVIg for therapeutic intervention. Primary cortical neurons were subjected to glucose deprivation (GD), oxygen-glucose deprivation (OGD) or simulated ischemia-reperfusion (I/R). Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion. Neurological assessment was performed, brain tissue damage was quantified, and NLRP1 and NLRP3 inflammasome protein levels were evaluated. NLRP1 and NLRP3 inflammasome components were also analyzed in postmortem brain tissue samples from stroke patients. Ischemia-like conditions increased the levels of NLRP1 and NLRP3 inflammasome proteins, and IL-1β and IL-18, in primary cortical neurons. Similarly, levels of NLRP1 and NLRP3 inflammasome proteins, IL-1β and IL-18 were elevated in ipsilateral brain tissues of cerebral I/R mice and stroke patients. Caspase-1 inhibitor treatment protected cultured cortical neurons and brain cells in vivo in experimental stroke models. IVIg treatment protected neurons in experimental stroke models by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity. Our findings provide evidence that the NLRP1 and NLRP3 inflammasomes have a major role in neuronal cell death and behavioral deficits in stroke. We also identified NLRP1 and NLRP3 inflammasome inhibition as a novel mechanism by which IVIg can protect brain cells against ischemic damage, suggesting a potential clinical benefit of therapeutic interventions that target inflammasome assembly and activity.
Although both theoretical predictions and experimental observations have demonstrated that the Gilbert damping is anisotropic at ferromagnet/semiconductor interface possessing robust interfacial ...spin-orbit coupling, it is not well understood whether non-local Gilbert damping driven by spin pumping in heavy metal/ferromagnetic metallic bilayers is anisotropic or not. Here, we investigated the angular and frequency dependence of magnetic relaxation in epitaxial Pd/Fe films on MgO(001) substrates. After disentangling parasitic contributions, we unambiguously observe that the non-local Gilbert damping is isotropic in the Fe(001) plane, suggesting that the spin transport across the Pd/Fe interface is independent of the Fe magnetization orientation. First principles calculations reveal that the effective spin mixing conductance of the Pd/Fe interface is nearly invariant for different magnetization directions, in good agreement with the experimental observations. These results offer valuable insight into spin transport in metallic bilayers, and facilitate the development of next-generation spintronic devices.
In single-molecule transistors, we observe inelastic cotunneling features that correspond energetically to vibrational excitations of the molecule, as determined by Raman and infrared spectroscopy. ...This is a form of inelastic electron tunneling spectroscopy of single molecules, with the transistor geometry allowing in situ tuning of the electronic states via a gate electrode. The vibrational features shift and change shape as the electronic levels are tuned near resonance, indicating significant modification of the vibrational states. When the molecule contains an unpaired electron, we also observe vibrational satellite features around the Kondo resonance.
Abstract
ASASSN-14ko is a recently discovered periodically flaring transient at the center of the active galactic nucleus (AGN) ESO 253−G003 with a slowly decreasing period. Here, we show that the ...flares originate from the northern, brighter nucleus in this dual-AGN, post-merger system. The light curves for the two flares that occurred in 2020 May and September are nearly identical over all wavelengths. For both events, Swift observations showed that the UV and optical wavelengths brightened in unison. The effective temperature of the UV/optical emission rises and falls with the increase and subsequent decline in the luminosity. The X-ray flux, by contrast, first rapidly drops over ∼2.6 days, rises for ∼5.8 days, drops again over ∼4.3 days, and then recovers. The X-ray spectral evolution of the two flares differ, however. During the 2020 May peak the spectrum softened with increases in the X-ray luminosity, while we observed the reverse for the 2020 September peak. We found a small change in the period derivative, which seems to indicate that the system does not have a static period derivative and there is some stochasticity in its evolution.
ABSTRACT
We report the phase-connected timing ephemeris, polarization pulse profiles, Faraday rotation measurements, and Rotating-Vector-Model (RVM) fitting results of 12 millisecond pulsars (MSPs) ...discovered with the Five-hundred-meter Aperture Spherical radio Telescope (FAST) in the Commensal Radio Astronomy FAST survey (CRAFTS). The timing campaigns were carried out with FAST and Arecibo over 3 yr. 11 of the 12 pulsars are in neutron star–white dwarf binary systems, with orbital periods between 2.4 and 100 d. 10 of them have spin periods, companion masses, and orbital eccentricities that are consistent with the theoretical expectations for MSP–Helium white dwarf (He WD) systems. The last binary pulsar (PSR J1912−0952) has a significantly smaller spin frequency and a smaller companion mass, the latter could be caused by a low orbital inclination for the system. Its orbital period of 29 d is well within the range of orbital periods where some MSP–He WD systems have shown anomalous eccentricities, however, the eccentricity of PSR J1912−0952 is typical of what one finds for the remaining MSP–He WD systems.
The Changing-look Blazar B2 1420+32 Mishra, Hora D.; Dai, Xinyu; Chen, Ping ...
The Astrophysical journal,
06/2021, Letnik:
913, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Abstract
Blazars are active galactic nuclei with their relativistic jets pointing toward the observer, comprising two major subclasses, flat-spectrum radio quasars (FSRQs) and BL Lac objects. We ...present multiwavelength photometric and spectroscopic monitoring observations of the blazar B2 1420+32, focusing on its outbursts in 2018–2020. Multiepoch spectra show that the blazar exhibited large-scale spectral variability in both its continuum and line emission, accompanied by dramatic gamma-ray and optical variability by factors of up to 40 and 15, respectively, on week to month timescales. Over the last decade, the gamma-ray and optical fluxes increased by factors of 1500 and 100, respectively. B2 1420+32 was an FSRQ with broad emission lines in 1995. Following a series of flares starting in 2018, it transitioned between BL Lac and FSRQ states multiple times, with the emergence of a strong Fe pseudocontinuum. Two spectra also contain components that can be modeled as single-temperature blackbodies of 12,000 and 5200 K. Such a collection of “changing-look” features has never been observed previously in a blazar. We measure gamma-ray–optical and interband optical lags implying emission-region separations of less than 800 and 130 gravitational radii, respectively. Since most emission-line flux variations, except the Fe continuum, are within a factor of 2–3, the transitions between FSRQ and BL Lac classifications are mainly caused by the continuum variability. The large Fe continuum flux increase suggests the occurrence of dust sublimation releasing more Fe ions in the central engine and an energy transfer from the relativistic jet to subrelativistic emission components.
Highlights • Donepezil inhibited mircoglial activation in APP/PS1 mice. • Donepezil reduced the level of proinflammatory cytokines in APP/PS1 mice. • Donepezil increased the expression of IDE, which ...is a degrading enzyme of Aβ. • Donepezil decreased insoluble Aβ40/Aβ42 and soluble Aβ40 levels in APP/PS1 mice. • The neuroprotection of donepezil may be due to its anti-inflammatory effects.
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