There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-$1{\beta}$ and tumor-necrosis factor-${\alpha}$ in the spinal cord of CCI rats. Bioinformatic analysis predicted that G protein-coupled receptor kinase 2 (GRK2), an important regulator in neuropathic pain and inflammation, was a potential target gene of miR-15a and miR-16. Inhibition of miR-15a and miR-16 markedly increased the expression of GRK2 while downregulating the activation of p38 mitogen-activated protein kinase and $NF-{\kappa}B$ in CCI rats. Notably, the silencing of GRK2 significantly reversed the inhibitory effects of miR-15a/16 inhibition in neuropathic pain. In conclusion, our results suggest that inhibition of miR-15a/16 expression alleviates neuropathic pain development by targeting GRK2. These findings provide novel insights into the molecular pathogenesis of neuropathic pain and suggest potential therapeutic targets for preventing neuropathic pain development.
Gloeostereum incarnatum has edible and medicinal value and was first cultivated and domesticated in China. We sequenced the G. incarnatum monokaryotic strain GiC-126 on an Illumina HiSeq X Ten system and obtained a 34.52-Mb genome assembly sequence that encoded 16,895 predicted genes. We combined the GiC-126 genome with the published genome of G. incarnatum strain CCMJ2665 to construct a genetic linkage map (GiC-126 genome) that had 10 linkage groups (LGs), and the 15 assembly sequences of CCMJ2665 were integrated into 8 LGs. We identified 1912 simple sequence repeat (SSR) loci and detected 700 genes containing 768 SSRs in the genome; 65 and 100 of them were annotated with gene ontology (GO) terms and KEGG pathways, respectively. Carbohydrate-active enzymes (CAZymes) were identified in 20 fungal genomes and annotated; among them, 144 CAZymes were annotated in the GiC-126 genome. The A mating-type locus (MAT-A) of G. incarnatum was located on scaffold885 at 38.9 cM of LG1 and was flanked by two homeodomain (HD1) genes, mip and beta-fg. Fourteen segregation distortion markers were detected in the genetic linkage map, all of which were skewed toward the parent GiC-126. They formed three segregation distortion regions (SDR1-SDR3), and 22 predictive genes were found in scaffold1920 where three segregation distortion markers were located in SDR1. In this study, we corrected and updated the genomic information of G. incarnatum. Our results will provide a theoretical basis for fine gene mapping, functional gene cloning, and genetic breeding the follow-up of G. incarnatum.
Objective: The objective of this study was to determine whether a dietary vitamin E (VE) supplement could alleviate any detrimental effects of aged corn on lipid metabolism and antioxidant status in laying hens. Methods: The experiment consisted of a 2×3 factorial design with two corn types (normal corn and aged corn (stored for 4 yr) and three concentrations of VE (0, 20, and 100 IU/kg). A total of 216 Lohmann laying hens (50 wk of age) were randomly allocated into six treatment diets for 12 wk. Each treatment had 6 replicates of 6 hens per replicate. Results: The results show that aged corn significantly decreased the content of low-density lipoprotein cholesterol (p<0.05), and reduced chemokine-like receptor 1 (CMKLR1) mRNA expression (p<0.05) in the liver compared to controls. Diet with VE did not alter the content of crude fat and cholesterol (p>0.05), or acetyl-CoA carboxylase, lipoprotein lipase, fatty acid synthase or CMKLR1 mRNA expression (p>0.05) in the liver among treatment groups. Aged corn significantly increased the content of malondialdehyde (MDA) (p<0.05) and decreased superoxide dismutase (SOD) activity (p<0.05) in the liver. The VE increased the content of MDA (p<0.05) but decreased glutathione peroxidase (GSH-Px) activity in serum (p<0.01) and in the ovaries (p<0.05). Adding VE at 20 and 100 IU/kg significantly increased GSH-Px activity (p<0.05) in liver and in serum (p<0.01), 100 IU/kg VE significantly increased SOD activity (p<0.05) in serum. Aged corn had no significant effects on GSH-Px mRNA or SOD mRNA expression (p<0.01) in the liver and ovaries. Addition of 100 IU/kg VE could significantly increase SOD mRNA expression (p<0.01) in the liver and ovary. Conclusion: Aged corn affected lipid metabolism and decreased the antioxidant function of laying hens. Dietary VE supplementation was unable to counteract the negative effects of aged corn on lipid metabolism. However, addition of 100 IU/kg VE prevented aged corninduced lipid peroxidation in the organs of laying hens.
BACKGROUND/OBJECTIVES: This study aimed to establish a mother and child cohort in the Chinese population, and investigate human breastmilk (HBM) composition and its relationship with maternal body mass index (BMI) and infant growth during the first 3 mon of life. SUBJECTS/METHODS: A total of 101 Chinese mother and infant pairs were included in this prospective cohort. Alterations in the milk macronutrients of Chinese mothers at 1 mon (T1), 2 mon (T2), and 3 mon (T3) lactation were analyzed. HBM fatty acid (FA) profiles were measured by gas chromatography (GC), and HBM proteomic profiling was achieved by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). RESULTS: During the first 3 mon of lactation (P < 0.05), significant decreases were determined in the levels of total energy, fat, protein, and osteopontin (OPN), as well as ratios of long-chain saturated FA (including C16:0, C22:0 and C24:0), monounsaturated FA (including C16:1), and n-6 poly unsaturated FA (PUFA) (including C20:3n-6 and C20:4n-6, and n-6/n-3). Conversely, butyrate, C6:0 and n-3 PUFA C18:3n-3 (α-linolenic acid, ALA) were significantly increased during the first 3 mon (P < 0.05). HBM proteomic analyses distinguished compositional protein differences over time (P = 0.001). Personalized motherinfant analyses demonstrated that HBM from high BMI mothers presented increased total energy, fat, protein and OPN, and increased content of n-6 PUFA (including C18:3n-6, C20:3n-6 and n-6/n-3 ratio) as compared with low BMI mothers (P < 0.05). Furthermore, BMI of the mothers positively correlated with the head circumference (HC) of infants as well as the specific n-6 PUFA C20:3n-6 over the 3 time points examined. Infant HC was negatively associated with C18:0. CONCLUSION: This study provides additional evidence to the Chinese HBM database, and further knowledge of FA function. It also helps to establish future maternal strategies that support the healthy growth and development of Chinese infants.
With the development of photovoltaic industry, the cost of photovoltaic power generation has become the significant issue. And the metallization process has decided the cost of original materials and photovoltaic efficiency of the solar cells. Nowadays, double printing process has been introduced instead of one-step printing process for front contact of polycrystalline silicon solar cells, which can effectively improve the photovoltaic conversion efficiency of silicon solar cells. Here, the relative cheap Cu paste has replaced the expensive Ag paste to form Ag/Cu composite front contact of silicon solar cells. The photovoltaic performance and the cost of photovoltaic power generation have been investigated. With the optimization on structure and height of Cu finger layer for Ag/Cu composite double-printed front contact, the silicon solar cells have exhibited a photovoltaic conversion efficiency of 18.41%, which has reduced 3.42 cent per Watt for the cost of photovoltaic power generation.
A method aimed at improving the beam-wave interaction efficiency by changing the coupling slot configuration has been proposed in the study of extended interaction oscillators (EIOs). The dispersion characteristics, coupling coefficient and interaction impedance of the high-frequency structure based on different types of coupling slots have been investigated. Four types of coupled cavity structures with different layouts of the coupling slots have been compared to improve the beam-wave interaction efficiency, so as to analyze the beam-wave interaction and practical applications. In order to determine the improvement of the coupling slot to a coupled cavity circuit in an EIO, we designed four nine-gap EIOs based on the coupled cavity structure with different coupling slot configurations. With different operating frequencies and voltages takes into consideration, beam voltages from 27 to 33 kV have been simulated to achieve the best beam-wave interaction efficiency so that the EIOs are able to work in the $2{\pi}$ mode. The influence of the Rb and the ds on the output power is also taken into consideration. The Rb is the radius of the electron beam, and the ds is the width of the coupling slot. The simulation results indicate that a single-slot-type EIO has the best beam-wave interaction efficiency. Its maximum output power is 2.8 kW and the efficiency is 18% when the operating voltage is 31 kV and electric current is 0.5 A. The output powers of these four EIOs that were designed for comparison are not less than 1.7 kW. The improved coupling-slot configurations enables the extended interaction oscillator to meet the different engineering requirements better.
Background: Postherpetic neuralgia (PHN) is the most common complication of acute herpes zoster. The treatment of PHN remains a challenge for clinical pain management. Despite the effectiveness of anticonvulsants, antidepressants, and lidocaine patches in reducing PHN, many patients still face intractable pain disorders. In this randomized controlled study, we evaluated whether hydromorphone through intravenous patient-controlled analgesia (IV PCA) was effective in relieving PHN. Methods: Patients with PHN were randomly divided into two groups, one group received oral pregabalin with IV normal saline, another group received oral pregabalin with additional IV PCA hydromorphone for two weeks. Efficacy was evaluated at 1, 4, and 12 weeks after the end of the treatments. Results: Two hundred and one patients were followed up for 12 weeks. After treatment, numerical rating scale (NRS) score of patients in the hydromorphone group was significantly lower than that of the control group, and the difference of NRS scores between the two groups was statistically significant at 4 and 12 weeks after treatment. The frequency of breakthrough pain in the hydromorphone group was significantly lower than that in the control group 1 and 4 weeks after treatment. After treatment, the quality of sleep in the hydromorphone group was significantly improved compared with the control group. The most common adverse reactions in the hydromorphone group were dizziness and nausea, with no significant respiratory depression. Conclusions: IV PCA hydromorphone combined with oral pregabalin provides superior pain relief in patients with PHN, which is worthy of clinical application and promotion.
Background: Panax ginseng Meyer (P. ginseng), a herb distributed in Korea, China and Japan, exerts benefits on diverse inflammatory conditions. However, the underlying mechanism and active ingredients remains largely unclear. Herein, we aimed to explore the active ingredients of P. ginseng against inflammation and elucidate underlying mechanisms. Methods: Inflammation model was constructed by lipopolysaccharide (LPS) in C57BL/6 mice and RAW264.7 macrophages. Molecular docking, molecular dynamics, surface plasmon resonance imaging (SPRi) and immunofluorescence were utilized to predict active component. Results: P. ginseng significantly inhibited LPS-induced lung injury and the expression of proinflammatory factors, including TNF-α, IL-6 and IL-1β. Additionally, P. ginseng blocked fluorescencelabeled LPS (LPS488) binding to the membranes of RAW264.7 macrophages, the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). Furthermore, molecular docking demonstrated that ginsenoside Ro (GRo) docked into the LPS binding site of toll like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex. Molecular dynamic simulations showed that the MD2-GRo binding conformation was stable. SPRi demonstrated an excellent interaction between TLR4/ MD2 complex and GRo (KD value of 1.16 × 10-9 M). GRo significantly inhibited LPS488 binding to cell membranes. Further studies showed that GRo markedly suppressed LPS-triggered lung injury, the transcription and secretion levels of TNF-α, IL-6 and IL-1β. Moreover, the phosphorylation of NF-κB and MAPKs as well as the p65 subunit nuclear translocation were inhibited by GRo dose-dependently. Conclusion: Our results suggest that GRo exerts anti-inflammation actions by direct inhibition of TLR4 signaling pathway.
Objective: In this study we aimed to evaluate the effect of dietary live yeast supplementation on ruminal pH pattern, fermentation characteristics and associated bacteria in beef cattle. Methods: This work comprised of in vitro and in vivo experiments. In vitro fermentation was conducted by incubating 0%, 0.05%, 0.075%, 0.1%, 0.125%, and 0.15% active dried yeast (Saccharomyces cerevisiae, ADY) with total mixed ration substrate to determine its dose effect. According to in vitro results, 0.1% ADY inclusion level was assigned in in vivo study for continuously monitoring ruminal fermentation characteristics and microbes. Six ruminally cannulated steers were randomly assigned to 2 treatments (Control and ADY supplementation) as two-period crossover design (30-day). Blood samples were harvested before-feeding and rumen fluid was sampled at 0, 3, 6, 9, and 12 h post-feeding on 30 d. Results: After 24 h in vitro fermentation, pH and gas production were increased at 0.1% ADY where ammonia nitrogen and microbial crude protein also displayed lowest and peak values, respectively. Acetate, butyrate and total volatile fatty acids concentrations heightened with increasing ADY doses and plateaued at high levels, while acetate to propionate ratio was decreased accordingly. In in vivo study, ruminal pH was increased with ADY supplementation that also elevated acetate and propionate. Conversely, ADY reduced lactate level by dampening Streptococcus bovis and inducing greater Selenomonas ruminantium and Megasphaera elsdenii populations involved in lactate utilization. The serum urea nitrogen decreased, whereas glucose, albumin and total protein concentrations were increased with ADY supplementation. Conclusion: The results demonstrated dietary ADY improved ruminal fermentation dose-dependently. The ruminal lactate reduction through modification of lactate metabolic bacteria could be an important reason for rumen pH stabilization induced by ADY. ADY supplementation offered a complementary probiotics strategy in improving gluconeogenesis and nitrogen metabolism of beef cattle, potentially resulted from optimized rumen pH and fermentation.
KIPS Transactions on Software and Data Engineering
/
v.11
no.1
/
pp.1-10
/
2022
Deep neural networks are widely used to solve various problems. In a fully connected neural network, the nonlinear activation function is a function that nonlinearly transforms the input value and outputs it. The nonlinear activation function plays an important role in solving the nonlinear problem, and various nonlinear activation functions have been studied. In this study, we propose a combined parametric activation function that can improve the performance of a fully connected neural network. Combined parametric activation functions can be created by simply adding parametric activation functions. The parametric activation function is a function that can be optimized in the direction of minimizing the loss function by applying a parameter that converts the scale and location of the activation function according to the input data. By combining the parametric activation functions, more diverse nonlinear intervals can be created, and the parameters of the parametric activation functions can be optimized in the direction of minimizing the loss function. The performance of the combined parametric activation function was tested through the MNIST classification problem and the Fashion MNIST classification problem, and as a result, it was confirmed that it has better performance than the existing nonlinear activation function and parametric activation function.
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