Soft actuators that can operate at high temperatures are of great interest in emerging research fields such as microfluidics, soft robotics, automotive, aircraft, and bioelectronics. However, most ...polymer-based flexible actuators suffer from performance degradation at elevated temperatures above 60 °C. In this paper, we present the high-temperature electromechanical actuation of relaxor ferroelectric polymers solution-blended with normal ferroelectric polymers. We conduct a systematic analysis of the electromechanical properties of three unimorph actuators with relaxor ferroelectric poly(vinylidene fluoride-trifluoroethylene-chlorofluoroethylene)s P(VDF-TrFE-CFE)s containing different amounts of chlorofluoroethylene (CFE) moieties (approximately 1, 3.5, and 9 wt%). In this study, we propose the film stress, given as Young's modulus times strain, as the measure of the electromechanical performance of soft bending actuators under loading, rather than strain or strain energy density. We demonstrate that a relaxor ferroelectric actuator with 1-wt% CFE, which mixes high-modulus ferroelectric crystal domains with an optimized electrostrictive relaxor phase, develops a high film stress of ∼3.5 MPa. When blended with the normal ferroelectric P(VDF-TrFE), the actuator exhibits excellent film stress of approximately 3.1 MPa at an elevated temperature of 60 °C comparable with that at 25 °C. The high-modulus ferroelectric crystals in P(VDF-TrFE) reinforce the mechanical properties of the actuator at elevated temperatures, generating high-temperature electromechanical actuation with a large strain and strain energy density of approximately 1.6% and 23 mJ/cm², respectively. We also demonstrate successful microfluidic pump operation at 60°C with our actuator using a relaxor ferroelectric polymer blended with an intrinsic ferroelectric polymer.
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Human noroviruses (HuNoVs) are a leading cause of gastroenteritis outbreaks worldwide. However, the paucity of appropriate cell culture models for HuNoV replication has prevented developing effective ...anti-HuNoV therapies. In this study, first, the replication of the virus at various temperatures in different cells was compared, which showed that lowering the culture temperature from 37°C significantly increased virus replication in Madin-Darby canine kidney (MDCK) cells. Second, the expression levels of autophagy-, immune-, and apoptosis-related genes at 30°C and 37°C were compared to explore factors affecting HuNoV replication. HuNoV cultured at 37°C showed significantly increased autophagy-related genes (ATG5 and ATG7) and immune-related genes (IFNA, IFNB, ISG15, and NFKB) compared to mock. However, the virus cultured at 30°C showed significantly decreased expression of autophagy-related genes (ATG5 and ATG7), but not significantly different major immune-related genes (IFNA, ISG15, and NFKB) compared to mock. Importantly, expression of the transcription factor FOXO1, which controls autophagy- and immune-related gene expression, was significantly lower at 30°C. Moreover, FOXO1 inhibition in temperature-optimized MDCK cells enhanced HuNoV replication, highlighting FOXO1 inhibition as an approach for successful virus replication. In the temperature-optimized cells, various HuNoV genotypes were successfully replicated, with GI.8 showing the highest replication levels followed by GII.1, GII.3, and GII.4. Furthermore, ultrastructural analysis of the infected cells revealed functional HuNoV replication at low temperature, with increased cellular apoptosis and decreased autophagic vacuoles. In conclusion, temperature-optimized MDCK cells can be used as a convenient culture model for HuNoV replication by inhibiting FOXO1 and providing adaptability to different genotypes.
Aging is associated with increased fat mass and elevated serum leptin levels (hyperleptinemia), causing proinflammation in the kidneys where it plays a primary role in the removal of endogenous ...leptin from the circulation. Lymphocyte-specific kinase (Lck) is a positive regulator of inflammatory signaling and a potential treatment target for age-related diseases, but its role in leptin signaling is unknown. Here, we investigated how Lck influences hyperleptinemia-induced inflammation in kidney tissues from 6- and 21-month-old rats. Results indicate that Lck expression and activation increased significantly in aged rat kidneys, especially at renal tubules. Furthermore, we identified interactions between Lck and short leptin-receptor isoforms, suggesting that Lck is a protein tyrosine kinase regulating leptin signaling. We further investigated whether increased Lck expression in renal tubular epithelial cells and macrophage infiltration are associated with leptin-induced inflammation. We then demonstrated that leptin activates Lck and proinflammatory transcription factors (STAT3 and NF-kappaB), while Lck knockdown modulates the expression of both transcription factors. Collectively, these data implicate that Lck leads to development of leptin-induced renal inflammation during aging. Inhibition of this protein tyrosine kinase may therefore be an appropriate therapeutic option for protection against age-related hyperleptinemia. Key words: Aging, Leptin; Lck, STAT3, NF-kappaB
Bee venom (BV), also known as apitoxin, is widely used in traditional oriental medicine to treat immune-related diseases. Recent studies suggest that BV could be beneficial for the treatment of ...neurodegenerative diseases. Parkinson’s disease (PD) is the second most common neurodegenerative disease next to Alzheimer’s disease, and PD pathologies are closely associated with neuroinflammation. Previous studies have suggested the neuroprotective effects of BV in animal models of PD are due to the modulation of inflammation. However, the molecular mechanisms responsible for the anti-neuroinflammatory effect of BV have not been elucidated in astrocytes. Here, the authors investigated the neuroprotective effects of BV and pramipexole (PPX; a positive control) in a subchronic MPTP-induced murine PD model. Both BV and PPX prevented MPTP-induced impairments in motor performance and reduced dopaminergic neuron loss, and furthermore, these neuroprotective effects of BV and PPX were found to be associated with reduced astroglial activation in vivo PD model. However, in MPP
+
treated primary cultured astrocytes, BV modulated astrocyte activation, whereas PPX did not, indicating that the neuroprotective effects of PPX were not mediated by neuroinflammation. These findings suggest that BV should be considered a potential therapeutic or preventive agent for PD and other neuroinflammatory associated disorders.
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, and is caused by the death of dopamine neurons and neuroinflammation in the striatum and substantia nigra. Furthermore, ...the inflammatory response in PD is closely related to glial cell activation. This study examined the neuroprotective effects of the barbiturate derivative, MHY2699 5-(4-hydroxy 3,5-dimethoxybenzyl)-2 thioxodihydropyrimidine-4,6(1H,5H)-dione in a mouse model of PD. MHY2699 ameliorated MPP⁺-induced astrocyte activation and ROS production in primary astrocytes and inhibited the MPP⁺-induced phosphorylation of MAPK and NF-κB. The anti-inflammatory effects of MHY2699 in protecting neurons were examined in an MPTP-induced mouse model of PD. MHY2699 inhibited MPTP-induced motor dysfunction and prevented dopaminergic neuronal death, suggesting that it attenuated neuroinflammation. Overall, MHY2699 has potential as a neuroprotective treatment for PD.
•DADS inhibited the proliferation of newly generated cells in the hippocampus.•DADS decreased the levels of ERK and BDNF-CREB signaling in the hippocampus.•DADS reduced memory retention observed in ...mice treated with high-dose.•High-dose DADS has adverse effects on hippocampal neurogenesis and neurocognitive function.
Garlic and garlic extracts are used as seasonings and are generally considered beneficial to human health, which include antioxidant and neuroprotective properties in neurological disorders. In the present study, we examined the effects of garlic sulfur components on the proliferation of neural progenitor cells (NPCs) and hippocampal neurogenesis. Of the sulfur compounds extracted, diallyl disulfide (DADS) significantly suppressed the proliferation of NPCs, whereas other sulfur containing components had no effect. In order to investigate the effect of DADS on adult hippocampal neurogenesis, DADS was administered orally to young (6 week-old) male C57BL/6 mice for 2 weeks. It was found that 10mg/kg of DADS significantly decreased the proliferation of NPCs in the dentate gyrus without affecting the survival of newly generated cells. Furthermore, DADS decreased levels of hippocampal BDNF, phosphorylated CREB signaling, and phosphorylated ERKs, which are known to be related to hippocampal neurogenesis and NPCs proliferation. In addition, DADS induced significant memory defects as compared with controls. We report that DADS may have adverse effects on hippocampal neurogenesis and neurocognitive functions by modulating ERK and BDNF-CREB signaling, and suggest that the advisability of consuming large amounts of garlic products should be considered, particularly during the period of neural growth.
Dense nuclear matter is ubiquitous in modern nuclear physics because it is related to many interesting microscopic and macroscopic phenomena such as heavy ion collisions, nuclear structure, and ...neutron stars. The on-going rare isotope science project in Korea will build up a rare isotope accelerator complex called RAON. One of the main goals of RAON is to investigate rare isotope physics including dense nuclear matter. Using the relativistic Boltzmann-Uehling-Uhlenbeck (RBUU) transport code, we estimate the properties of nuclear matter that can be created from low-energy heavyion collisions at RAON.We give predictions for the maximum baryon density, the isospin asymmetry and the temperature of nuclear matter that would be formed during
197
Au+
197
Au and
132
Sn+
64
Ni reactions. With a large isospin asymmetry, various theoretical studies indicate that the critical densities or temperatures of phase transitions to exotic states decrease. Because a large isospin asymmetry is expected in the dense matter created at RAON, we discuss possibilities of observing exotic states of dense nuclear matter at RAON for large isospin asymmetry.
Abstract
Background
It has recently been demonstrated that HDAC6 depletion ameliorates the impairment of memory function and mitochondrial axonal transport induced by the accumulation of Aβ. However, ...very little is known about molecular mechanisms through which HDAC6 regulates APP processing. Also, it remains controversial whether HDAC6 induces inflammation or reduces it.
Method
We analyzed the expression of HDAC6 in AD patients and 5xFAD mice. We confirmed that HDAC6 regulates BACE1 in primary neurons and NLRP3 inflammasome in primary microglia. And we crossed HDAC6 knock‐out mice with 5xFAD mice and got 5xFAD/HDAC6 KO. We compared 5xFAD (n = 11) and 5xFAD/HDAC6 KO (n = 13). We did a nest building test, open field test, Morris water maze, Y‐maze, passive avoidance, and elevated plus maze. After finishing all these behaviour tests, we sacrificed the mouse and checked protein and mRNA. We did Immunohistochemistry using Aβ plaque, NLRP3 inflammasome and synapse‐related markers. We also did RNA‐seq analysis in these mice’s brains.
Result
We confirmed that the expression of HDAC6 was increased in the AD cortex compared to neuropathologically normal brains. The stability of BACE1 is regulated by its C‐terminal lysine, and HDAC6 deacetylates the C‐terminal lysine of BACE1 by direct binding. Also, HDAC6 deficiency reduced NLRP3 inflammasome activation‐, and subsequent inflammatory responses in microglia. By crossing HDAC6 knock‐out mice with 5xFAD mice, the role of HDAC6 was confirmed in an animal model of AD. HDAC6 deletion improved cognitive function and reduced the protein expression of BACE1 and inflammatory factors in 5xFAD mice. Also, HDAC6‐deficient 5xFAD mice developed fewer dense‐core plaques, IL‐1β, and ASC specks than 5xFAD mice. Furthermore, RNA‐sequencing was analyzed from the hippocampus of 5xFAD and 5xFAD/HDAC6 KO mice. Synapse and neuron development‐related genes were significantly up‐regulated, and type I interferon, immune response, and prion disease‐related genes were down‐regulated in HDAC6‐depleted mice. Finally, we confirmed that the ratio of PSD95 colocalized with C1q was significantly decreased in 5xFAD/HDAC6 KO compared to 5xFAD mice, which suggested that synapse loss was inhibited in AD mice.
Conclusion
This study reveals distinct functions of HDAC6 and suggests HDAC6 as a significant regulator in the pathogenesis of AD that could be exploited therapeutically.
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