A novel miniaturised dual-band bandpass filter (BPF) based on defected split-ring resonators (SRRs) and irregular stepped-impedance resonators (SIRs) is proposed. By applying defected SRRs embedded ...with eight combinations of three whole or broken grooves, which are formerly used for divination, the passband of 2.35–2.52 GHz with wideband harmonic suppression is achieved for WLAN applications. To create one more passband of 5.09–5.3 GHz, the irregular SIRs are etched inside the defected SRRs. Finally, such a prototype is designed and fabricated with the dimension of only 20 × 20 mm2 (0.27λg × 0.27λg). The measured results of this dual-band BPF agree well with the simulations verifying the proposed idea.
Adult neurogenesis plays a vital role in maintaining cognitive functions in mammals and human beings. Mobilization of hippocampal neurogenesis has been regarded as a promising therapeutic approach to ...restore injured neurons in neurodegenerative diseases including Alzheimer's disease (AD). Icarisid II (ICS II), an active ingredient derived from Epimedii Folium, has been reported to exhibit multiple neuroprotective effects. In the present study, we investigated the effects of ICS II on the proliferation and differentiation of neural stem cells (NSCs) and amyloid precusor protein (APP)‐overexpressing NSCs (APP‐NSCs) in vitro. Our results demonstrated that ICS II dose‐dependently suppressed apoptosis and elevated viability of APP‐NSCs. ICS II (1 μM) potently promoted proliferation and neuronal differentiation of NSCs and APP‐NSCs. ICS II (1 μM) significantly upregulated Wnt‐3a expression, increased the phosphorylation of glycogen synthase kinase‐3β and enhanced the nuclear transfer of β‐catenin. Moreover, ICS II also promoted astrocytes to secrete Wnt‐3a, which positively modulates Wnt/β‐catenin signaling pathway. These findings demonstrate that ICS II promotes NSCs proliferation and neuronal differentiation partly by activating the Wnt/β‐catenin signaling pathway.
•For the first time quarternary phosphonium IL grafted on biopolymer CS, CS-BuPh3PBr, was fabricated.•CS-BuPh3PBr was used as catalyst for the cycloaddition reaction.•CS-BuPh3PBr shows good catalytic ...activity, stability and recyclability.•The good activity is attributed to synergistic effect of OH, P cations, and Br–.
We prepared chitosan-grafted quarternary phosphonium ionic liquid (1-butyl-triphenylphosphonium bromide) by a simple method and used it as catalyst for the synthesis of cyclic carbonates through CO2 cycloaddition to epoxides in the absence of co-catalyst and solvent. High yield of propylene carbonate (96.3%) is obtained at 120°C and 2.5MPa in 4h. We studied the roles of chitosan hydroxyl groups and ionic liquid counter anions on catalytic activity. It is proposed that the facilitation of ring opening of epoxides is a combined result of polarization (by hydrogen bonding due to hydroxyl groups), electronic interaction (by BuPh3P+), and nucleophilic attack (by bromide anion). The catalyst can be easily recovered and reused as demonstrated in a test of five runs without showing any significant loss of activity. From the view point of commercial application, the catalyst is attractive because it is low-cost, ecology-safe, stable and efficient. Furthermore, it is potentially applicable for fixed-bed continuous flow reactors.
Background and Purpose:
Temporal lobe epilepsy (TLE) is a common chronic neurological disease that is often invulnerable to anti-epileptic drugs. Increasing data have demonstrated that acetylcholine ...(ACh) and cholinergic neurotransmission are involved in the pathophysiology of epilepsy. Cytisine, a full agonist of α7 nicotinic acetylcholine receptors (α7nAChRs) and a partial agonist of α4β2nAChRs, has been widely applied for smoking cessation and has shown neuroprotection in neurological diseases. However, whether cytisine plays a role in treating TLE has not yet been determined.
Experimental Approach:
In this study, cytisine was injected intraperitoneally into pilocarpine-induced epileptic rats for three weeks. Alpha-bungarotoxin (α-bgt), a specific α7nAChR antagonist, was used to evaluate the mechanism of action of cytisine. Rats were assayed for the occurrence of seizures and cognitive function by video surveillance and Morris water maze. Hippocampal injuries and synaptic structure were assessed by Nissl staining and Golgi staining. Furthermore, levels of glutamate, γ-aminobutyric acid (GABA), ACh, and α7nAChRs were measured.
Results:
Cytisine significantly reduced seizures and hippocampal damage while improving cognition and inhibiting synaptic remodeling in TLE rats. Additionally, cytisine decreased glutamate levels without altering GABA levels, and increased ACh levels and α7nAChR expression in the hippocampi of TLE rats. α-bgt antagonized the above-mentioned effects of cytisine treatment.
Conclusion and Implications:
Taken together, these findings indicate that cytisine exerted an anti-epileptic and neuroprotective effect in TLE rats via activation of α7nAChRs, which was associated with a decrease in glutamate levels, inhibition of synaptic remodeling, and improvement of cholinergic transmission in the hippocampus. Hence, our findings not only suggest that cytisine represents a promising anti-epileptic drug, but provides evidence of α7nAChRs as a novel therapeutic target for TLE.
Lymphatic metastasis is a common clinical symptom in nasopharyngeal carcinoma (NPC), the most common Epstein-Barr virus (EBV)-associated head and neck malignancy. However, the effect of EBV on NPC ...lymph node (LN) metastasis is still unclear. In this study, we demonstrated that EBV infection is strongly associated with advanced clinical N stage and lymphangiogenesis of NPC. We found that NPC cells infected with EBV promote LN metastasis by inducing cancer-associated lymphangiogenesis, whereas these changes were abolished upon clearance of EBV genomes. Mechanistically, EBV-induced VEGF-C contributed to lymphangiogenesis and LN metastasis, and PHLPP1, a target of miR-BART15, partially contributed to AKT/HIF1a hyperactivity and subsequent VEGF-C transcriptional activation. In addition, administration of anti-VEGF-C antibody or HIF1α inhibitors attenuated the lymphangiogenesis and LN metastasis induced by EBV. Finally, we verified the clinical significance of this prometastatic EBV/VEGF-C axis by determining the expression of PHLPP1, AKT, HIF1a, and VEGF-C in NPC specimens with and without EBV. These results uncover a reasonable mechanism for the EBV-modulated LN metastasis microenvironment in NPC, indicating that EBV is a potential therapeutic target for NPC with lymphatic metastasis. IMPLICATIONS: This research demonstrates that EBV induces lymphangiogenesis in NPC by regulating PHLPP1/p-AKT/HIF1a/VEGF-C, providing a new therapeutic target for NPC with lymphatic metastasis.
Caveolin-3 (CAV3) protein is known to be expressed specifically in various myocytes, but its physiological function remains unclear. CAV3, located at the cell membrane, may promote the sensitivity of ...the Akt signaling pathway, which is closely related to glucose metabolism and to cell growth and proliferation.
The CAV3 gene was stably transfected into C2C12 muscle cells, and the effects were evaluated by biochemical assays, WB and confocal microscopy for the observation of cellular glucose metabolism, growth and proliferation, and the effect of CAV3 on the Akt signaling pathway with no insulin stimulation.
After C2C12 cells were transfected with the mouse CAV3 gene, which increased CAV3 expression, the abundance of the CAV3 and GLUT4 proteins on the cell membrane increased, but the total GLUT4 protein content of the cell was unchanged. Glucose uptake was increased, and this did not affect the glycogen synthesis, but the cell surface area and cell proliferation increased. While there were significant increases in p-Akt and p-p70s6K, which is a downstream component of Akt signaling, the level of GSK3β protein, another component of Akt signaling did not change.
The muscle, CAV3 protein can activate Akt signaling, increase GLUT4 protein localization in the cell membrane, increase glucose uptake, and promote myocyte growth and proliferation. CAV3 protein has a physiological role in glycometabolism, growth and proliferation, independent of insulin stimulation.
Oligoasthenoteratozoospermia (OAT) is characterized as low sperm count, decreased sperm motility and structural abnormalities of the sperm head in the same patient. However, very few studies reported ...the genetic alterations associated with OAT. Here we report a 38-year-old patient with OAT from a consanguineous family, with 2–6 million/mL sperm density, 2.1–3.8% normal sperm morphology and immotile sperm. Whole-exome sequencing (WES) identified homozygous variant c.1259A>G:p.Y420C in the TDRD6 gene. TDRD6 is a testis-specific expressed protein that was localized to the chromatoid bodies in germ cells and played an important role in the nonsense-mediated decay pathway. This rare variant co-segregated with the OAT phenotype in this family. Bioinformatic analysis also suggested the variant a pathogenic mutation. Two intracytoplasmic sperm injection (ICSI) cycles were carried out in the patient's wife, but she did not become pregnant after embryo transfer. So the mutations in TDRD6 may be associated with human male infertility and early embryonic lethality.
•We identified a novel gene (TDRD6) and mutation that is associated with oligoasthenoteratozoospermia.•Whole-exome sequencing (WES) identified a homozygous mutation in the TDRD6 gene (c.1259A>G:p.Y420C).•The mutation was also associated with early embryonic lethality.
Abstract The aim of this study was to explore the effect by which the combination of Astragaloside IV (AST IV) and Ginsenoside Rg1 (Rg1) resisted autophagic injury in PC12 cells induced by oxygen ...glucose deprivation/reoxygenation (OGD/R). We studied the nature of the interaction between AST IV and Rg1 that inhibited autophagy through the Isobologram method, and investigated the synergistic mechanism via the PI3K I/Akt/mTOR and PI3K III/Becline-1/Bcl-2 signaling pathways. Our results showed that, based on the 50% inhibiting concentration (IC50), AST IV combined with Rg1 at a 1:1 ratio resulted in a synergistic effect, whereas the combination of the two had an antagonistic effect on autophagy at ratios of 1:2 and 2:1. Meanwhile, AST IV and Rg1 alone increased cell survival and decreased lactate dehydrogenase (LDH) leakage induced by OGD/R, reduced autophagosomes and the LC3 II positive patch, down-regulated the LC3 II/LC3 I ratio and up-regulated the p62 protein; the 1:1 combination enhanced these effects. Mechanistic study showed that Rg1 and the 1:1 combination increased the phosphorylation of PI3K I, Akt and mTOR; the effects of the combination were greater than those of the drugs alone. AST IV and the 1:1 combination suppressed the expression of PI3K III and Becline-1, and the combination elevated Bcl-2 protein expression; the effects of the combination were better than those of the drugs alone. These results suggest that after 2 h-OGD followed by reoxygenation for 24 h, PC12 cells suffer excessive autophagy and damage, which are blocked by AST IV or Rg1; moreover, the combination of AST IV and Rg1 at a 1:1 ratio of their IC50 concentrations has a synergistic inhibition on autophagic injury. The synergistic mechanism may be associated with the PI3K I/Akt/mTOR and PI3K III/Becline-1/Bcl-2 signaling pathways.
To assess the association of socioeconomic status with the burden of cataract blindness in terms of year lived with disability (YLD) rates and to determine whether ultraviolet radiation (UVR) levels ...modify the effect of socioeconomic status on this health burden.
National and subnational age-standardized YLD rates associated with cataract-related blindness were derived from the Global Burden of Disease (GBD) study 2017. The human development index (HDI) from the Human Development Report was used as a measure of socioeconomic status. Estimated ground-level UVR exposure was obtained from the Ozone Monitoring Instrument (OMI) dataset of the National Aeronautics and Space Administration (NASA).
Across 185 countries, socioeconomic status was inversely associated with the burden of cataract blindness. Countries with a very high HDI had an 84% lower age-standardized YLD rate 95% confidence interval (CI): 60%–93%, P < 0.001 than countries with a low HDI; for high-HDI countries, the proportion was 76% (95% CI: 53%–88%, P < 0.001), and for medium-HDI countries, the proportion was 48% (95% CI: 15%–68%, P = 0.010; P for trend < 0.001). The interaction analysis showed that UVR exposure played an interactive role in the association between socioeconomic status and cataract blindness burden (P value for interaction = 0.047).
Long-term high-UVR exposure amplifies the association of poor socioeconomic status with the burden of cataract-related blindness. The findings emphasize the need for strengthening UVR exposure protection interventions in developing countries with high-UVR exposure.
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