Osteoarthritis (OA) is a complicated degenerative disease that affects whole joint tissue. Currently, apart from surgical approaches to treat late stage OA, effective treatments to reverse OA are not ...available. Thus, the mechanisms leading to OA, and more effective approaches to treat OA should be investigated. According to available evidence, the PI3K/AKT/mTOR signaling pathway is essential for normal metabolism of joint tissues, but is also involved in development of OA. To provide a wide viewpoint to roles of PI3K/AKT/mTOR signaling pathway in osteoarthritis, a comprehensive literature search was performed using PubMed terms ‘PI3K OR AKT OR mTOR’ and ‘osteoarthritis’. This review highlights the role of PI3K/AKT/mTOR signaling in cartilage degradation, subchondral bone dysfunction, and synovial inflammation, and discusses how this signaling pathway affects development of the disease. We also summarize recent evidences of therapeutic approaches to treat OA by targeting the PI3K/AKT/mTOR pathway, and discuss potential challenges in developing these strategies for clinical treatment of OA.
Nanoimprint lithography (NIL) is a nonconventional lithographic technique for high‐throughput patterning of polymer nanostructures at great precision and at low costs. Unlike traditional lithographic ...approaches, which achieve pattern definition through the use of photons or electrons to modify the chemical and physical properties of the resist, NIL relies on direct mechanical deformation of the resist material and can therefore achieve resolutions beyond the limitations set by light diffraction or beam scattering that are encountered in conventional techniques. This Review covers the basic principles of nanoimprinting, with an emphasis on the requirements on materials for the imprinting mold, surface properties, and resist materials for successful and reliable nanostructure replication.
Nanoimprint lithography (see figure) is an emerging lithographic technique for high‐throughput patterning of polymer nanostructures at high resolutions and low costs. This Review article considers the basic principles of nanoimprinting, with an emphasis on the requirements placed on materials to allow successful and reliable nanostructure replication.
Episodic memory deficits are consistently documented as a core aspect of cognitive dysfunction in schizophrenia patients, present from the onset of the illness and strongly associated with functional ...disability. Over the past decade, research using approaches from experimental cognitive neuroscience revealed disproportionate episodic memory impairments in schizophrenia (Sz) under high cognitive demand relational encoding conditions and relatively unimpaired performance under item-specific encoding conditions. These specific deficits in component processes of episodic memory reflect impaired activation and connectivity within specific elements of frontal-medial temporal lobe circuits, with a central role for the dorsolateral prefrontal cortex (DLPFC), relatively intact function of ventrolateral prefrontal cortex and variable results in the hippocampus. We propose that memory deficits can be understood within the broader context of cognitive deficits in Sz, where impaired DLPFC-related cognitive control has a broad impact across multiple cognitive domains. The therapeutic implications of these findings are discussed.
Influenza virus is a significant pathogen in humans and animals with the ability to cause extensive morbidity and mortality. Exuberant immune responses induced following infection have been described ...as a “cytokine storm,” associated with excessive levels of proinflammatory cytokines and widespread tissue damage. Recent studies have painted a more complex picture of cytokine networks and their contributions to clinical outcomes. While many cytokines clearly inflict immunopathology, others have non-pathological delimited roles in sending alarm signals, facilitating viral clearance, and promoting tissue repair, such as the IL-33—amphiregulin axis, which plays a key role in resolving some types of lung damage. Recent literature suggests that type 2 cytokines, traditionally thought of as not involved in anti-influenza immunity, may play an important regulatory role. Here, we discuss the diverse roles played by cytokines after influenza infection and highlight new, serene features of the cytokine storm, while highlighting the specific functions of relevant cytokines that perform unique immune functions and may have applications for influenza therapy.
We have combined hard X-ray photoelectron spectroscopy with angular dependent O K-edge and V L-edge X-ray absorption spectroscopy to study the electronic structure of metallic and insulating end ...point phases in 4.1 nm thick (14 units cells along the c-axis of VO2) films on TiO2(001) substrates, each displaying an abrupt MIT centered at ∼300 K with width <20 K and a resistance change of ΔR/R > 103. The dimensions, quality of the films, and stoichiometry were confirmed by a combination of scanning transmission electron microscopy with electron energy loss spectroscopy, X-ray spectroscopy, and resistivity measurements. The measured end point phases agree with their bulk counterparts. This clearly shows that, apart from the strain induced change in transition temperature, the underlying mechanism of the MIT for technologically relevant dimensions must be the same as the bulk for this orientation.
Magnetic reconnection is a fundamental plasma process that plays a critical role not only in energy release in the solar atmosphere, but also in fusion, astrophysics, and other space plasma ...environments. One of the challenges in explaining solar observations in which reconnection is thought to play a critical role is to account for the transition of the dynamics from a slow quasi-continuous phase to a fast and impulsive energetic burst of much shorter duration. Despite the theoretical progress in identifying mechanisms that might lead to rapid onset, a lack of observations of this transition has left models poorly constrained. High-resolution spectroscopic observations from NASA's Interface Region Imaging Spectrograph now reveal tell-tale signatures of the abrupt transition of reconnection from a slow phase to a fast, impulsive phase during UV bursts or explosive events in the Sun's atmosphere. Our observations are consistent with numerical simulations of the plasmoid instability, and provide evidence for the onset of fast reconnection mediated by plasmoids and new opportunities for remote-sensing diagnostics of reconnection mechanisms on the Sun.
Soil acidification is a major problem in soils of intensive Chinese agricultural systems. We used two nationwide surveys, paired comparisons in numerous individual sites, and several long-term ...monitoring-field data sets to evaluate changes in soil acidity. Soil pH declined significantly (P < 0.001) from the 1980s to the 2000s in the major Chinese crop-production areas. Processes related to nitrogen cycling released 20 to 221 kilomoles of hydrogen ion (H⁺) per hectare per year, and base cations uptake contributed a further 15 to 20 kilomoles of H⁺ per hectare per year to soil acidification in four widespread cropping systems. In comparison, acid deposition (0.4 to 2.0 kilomoles of H⁺ per hectare per year) made a small contribution to the acidification of agricultural soils across China.
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•A new refractory MoNbHfZrTi high-entropy alloy with single BCC phase is prepared.•The single disordered BCC phase has high structural stability.•The compressive yield strength is ...1719MPa at room temperature.•This alloy still has high compression yield strength at elevated temperatures.•The dynamic recrystallization occurs during elevated-temperature compression.
The present paper reports the microstructure, phase stability and mechanical properties of a new refractory MoNbHfZrTi high-entropy alloy. MoNbHfZrTi alloy consists of a disordered body-centered cubic (BCC) solid solution phase in as-cast and homogenized states. Homogenization treatment and DSC analysis indicate that there is no any phase transition below 1743K. At room temperature, the compressive yield strength for the alloy in as-cast and as-homogenized states reaches about 1719MPa and 1575MPa, respectively and the fracture mechanism is brittle quasi-cleavage fracture. At elevated temperatures, this alloy has compression yield strength of 825MPa at 1073K, 728MPa at 1173K, 635MPa at 1273K, 397MPa at 1373K and 187MPa at 1473K and some fine grains form at grain boundaries due to partial dynamic recrystallization.
Highlights • Gastrodin improves learning and memory abilities of Tg2576 mice. • Gastrodin attenuates intracellular oxidative stress in hippocampi of Tg2576 mice. • Gastrodin suppresses BACE1 ...expression and PKR/eIF2α pathway in hippocampi of Tg2576 mice. • Gastrodin suppresses BACE1 via inhibiting PKR/eIF2α in SH-SY5Y cells under oxidative stress.
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