Search

The Yiqi-Huoxue granule (YQHX) is a traditional Chinese medication widely used in the therapy of the traditional Chinese medicine diagnosis “Qi deficiency” or “blood stasis” in China. Both these symptoms are related to inflammation, but the mechanisms of YQHX against inflammation are largely unknown. Thus, our present study investigated the effects of YQHX on regulating inflammatory responses induced by lipopolysaccharides (LPS) in HUVECs. Our data found that YQHX remarkably inhibits the production of prothrombotic factors, plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF), while it upregulates the protein expression of Kruppel-like factor 2 (KLF2). The increase in PAI-1 and TF was significantly attenuated through a transgenic knockdown in KLF2 with a Lenti-shKLF2 vector. YQHX also decreases the phosphorylation of nuclear factor-κB (NF-κB) p65 and IκB following LPS stimulation, and it effectively suppresses PAI-1 and TF via a NF-κB-dependent mechanism. Taken together, our results suggest that YQHX provides a notable antithrombotic activity via regulating the KLF2 expression and NF-κB signaling pathway in HUVECs. The KLF2 and NF-κB may be potential therapeutic targets for interventions of inflammation associated with atherosclerosis.

The increase incidence of multi-drug resistant (MDR) Salmonella has become a major global health concern. Polymyxin, an ancient polypeptide antibiotic, has been given renewed attention over recent years, resulting in resistance of Gram-negative bacteria to polymyxin, but its resistance mechanism is not completely clear. Thus, it is important to study its resistance mechanisms. In this study, an in vitro induced polymyxin-resistant strain of Salmonella typhimurium in the laboratory were constructed to investigate the mechanism of resistance of Salmonella to polymyxin. Gradual induction of Salmonella typhimurium ATCC13311 (AT) by concentration increment was used to screen for a highly polymyxin-resistant strain AT-P128. The broth dilution technique was used to compare the sensitivity of the two strains to different antimicrobial drugs. Single nucleotide polymorphisms (SNPs) were then identified by whole genome sequencing, and differences in gene expression between the two strains were compared by transcriptome sequencing and reverse transcription-quantitative PCR (RT-qPCR). Finally, for the first time, the CRISPR/Cas9 gene-editing system was used to construct gene deletion mutants in Salmonella to knock out the phoP gene of AT-P128. The results showed that strain AT-P128 was significantly more resistant to amoxicillin, ceftiofur, ampicillin, fluphenazine, and chloramphenicol and significantly less resistant to sulfamethoxazole than the parental strain AT. The growth curve results showed no significant change in the growth rate between AT-P128 and AT. Motility and biofilm formation assays showed a significant decrease in AT-P128. Additionally, the WGS results showed that AT-P128 had mutations in 9 genes involving 14 SNPs. RNA-seq and RT-qPCR results showed increased expression of phoPQ. The loss of the phoP gene decreased AT-P128ΔphoP resistance to polymyxin by 32-fold. These results suggested that polymyxin resistance affected the biology, genome components, and gene expression levels of Salmonella and that the PhoPQ two-component system played a key role in polymyxin resistance in Salmonella, providing insights into the diversity and complexity of polymyxin resistance in Salmonella.

This Letter studies the effect of crystallinity on the performance of AlN-based resistive random access memory using rapid thermal annealing. We compared I–V characters of devices fabricated at different annealing temperatures. By increasing the crystallinity of an AlN film, switching voltages and the memory window increase. Meanwhile, the reliability of the device improves. It is found that the electron conduction mechanism fits in with the space-charge-limited conduction model. Based on the above phenomena, we purpose that the crystallization leads to a decrease in vacancies within the AlN film, while it enhances local effects of grain boundaries on the electron transport. Both of these conclusions can result in an increase in switching voltages and the memory window. This paper can provide a platform for further studies on improving the performance of AlN-based devices.

This Letter studies the effect of the nitrogen capture ability of quantum dots on resistive switching characteristics of AlN-based resistive random access memory. We prepared a single layer AlN device and four types of AlN/PbS quantum dot stacked structure devices with different concentrations. Compared with the single layer AlN device, the AlN/PbS quantum dot stacked structure devices exhibit excellent resistive switching characteristics, such as forming-free, low power consumption, and excellent stability. We propose that the resistive switching process is determined by the migration of nitrogen ions and the lead sulfide (PbS) quantum dot layer as a natural nitrogen ion reservoir, which can improve the resistive switching characteristics. Moreover, the size of the natural nitrogen ion reservoir can be modulated by changing the concentration of quantum dots.

When a simple system is in its nonequilibrium state, it will shift to its equilibrium state. Obviously, in this process, there are a series of nonequilibrium states. With the assistance of Bayesian statistics and hyperensemble, a probable probability distribution of these nonequilibrium states can be determined by maximizing the hyperensemble entropy. It is known that the largest probability is the equilibrium state, and the far a nonequilibrium state is away from the equilibrium one, the smaller the probability will be, and the same conclusion can also be obtained in the multi-state space. Furthermore, if the probability stands for the relative time the corresponding nonequilibrium state can stay, then the velocity of a nonequilibrium state returning back to its equilibrium can also be determined through the reciprocal of the derivative of this probability. It tells us that the far away the state from the equilibrium is, the faster the returning velocity will be; if the system is near to its equilibrium state, the velocity will tend to be smaller and smaller, and finally tends to 0 when it gets the equilibrium state.

Forsythia suspensa (Thunb.) Vahl leaves have been consumed in China as a health-promoting functional tea for centuries. Three new polyhydroxytriterpenoid glycosides named suspensanosides A-C (1-3), seven known polyhydroxytriterpenoids (4-10), and 12 known phenolics (11-22) were identified from F. suspensa leaves. Compounds 1-10, 15-17, and 22 have not been found in the Forsythia genus previously, whereas compound 14 was first reported to be isolated from the leaves of F. suspensa. All isolates were tested for their antiproliferative activities on BGC-823 and MCF-7 human tumor cell lines, whereas all phenolics were further investigated for their antioxidant activities by a DPPH assay. The results clearly demonstrate that triterpenoids, especially ursane-type triterpenoids, and the diverse phenolic components are crucial for the beneficial effects of F. suspensa leaves.

Applications in neuromorphic computing and next-generation memories require a deep understanding of the physical mechanisms in resistive switching (RS) devices. Here, we report electrode-induced polarity conversion in Nb2O5/NbOx RS devices, where Nb2O5 and NbOx are a switching layer and an oxygen vacancy ( V o · ·) reservoir, respectively. The reservoir provides the V o · · s, comprising a conductive filament formed during an electroforming process. After the process, the devices with an inert Pt top electrode show a clockwise RS behavior. However, the ones with a reactive W top electrode exhibit a counterclockwise RS behavior. Detailed explorations suggest that reactive electrodes provide an oxygen ion reservoir near the active region of the conductive filaments. The reservoir dominates the rupture and recovery of the conductive filaments through interfacial redox reaction, which induces the switching polarity conversion. This study indicates that oxygen ion distribution and migration near a conductive filament tip have the dominant effect on switching processes of oxide RS devices.

In this study, a regenerated nanotweezer-managed catalytic DNA circuit was constructed. A nanotweezer with two crossover motifs was assembled using 10 oligonucleotides, a toehold domain (TD), and a branch migration domain (BMD) as the two motifs of the nanotweezer. In the absence of a catalyst, the nanotweezer was opened, the TD and the BMD were separated with few catalytic activities. Upon catalyst addition, the set strand in the nanotweezer was liberated, forming a closed nanotweezer with proximal binding of the TD and the BMD with catalytic activity. Subsequently, the TD/BMD initiated the cyclic catalytic assembly of DNA hairpins, forming a DNA circuit. By re-introducing some set sequences, the nanotweezer and TD/BMD could be switched back to the opened state, and the progress of catalytic DNA circuit could be stopped and managed. By re-adding fresh catalysts, the stopped circuit could be re-initiated through regeneration of the closed nanotweezer. Thus, a controllable and flexible DNA circuit was achieved with sensitive and quantitative detection of cancer-related miRNA and uracil-DNA glycosylase (UDG) in complex biological samples. The novel system provid a flexible and reliable DNA circuit for biological detection, clinical diagnosis, and biomedical research.

Although the protective effects of Yiqi-Huoxue granule (YQHX), a Chinese 4-herb formula, on patients with ischemic heart diseases are related to the attenuation of oxidative stress injury, the mechanism(s) underlying these actions remains poorly understood.Our aim was to investigate the potential protective effects of YQHX treatment against oxidative stress induced by hydrogen peroxide (HH9c2 cells were treated with YQHX for 16 h before exposed to 200 μM HHTaken together, our study demonstrated that YQHX attenuates H

A quaternary ammonium gemini surfactant containing an ester spacer, namely (diethylhexanedioate)diyl-α,ω-bis(dimethyl myristyl ammonium bromide) (14-DEHA-14) was synthesized using a two-step procedure with dimethyl hexanedioate, dimethylaminoethanol, and 1-bromotetradecane. The chemical structure of the compound was confirmed by infrared (IR) spectrum, 1H nuclear magnetic resonance (NMR), and elemental analysis. The critical micelle concentration was determined by conductivity and tensiometry measurements, and its inhibition effect on corrosion of carbon steel in dilute (1.0 M) hydrochloric acid solution was investigated by weight loss measurements. The results show that the synthesized gemini surfactant acts as an excellent corrosion inhibitor in 1.0 M HCl solution. The adsorption of the inhibitor via chemical adsorption onto the carbon steel surface obeyed the Langmuir adsorption isotherm. A possible corrosion mechanism of the compound is discussed in relation to the calculated thermodynamic parameters and adsorption isotherm.

Background Preterm infants' repeated exposure to painful procedures may lead to negative consequences. Thus, non-pharmacological pain management is essential due to medication side effects. Kangaroo Mother Care, which aims at offering human care to neonates, has been established for the treatment of a single painful procedure, but the effectiveness of Kangaroo Mother Care across repeated painful procedures is unknown. Objective To test the effectiveness of repeated Kangaroo Mother Care on repeated heel-stick pain in preterm neonates. Design Randomized controlled trial. Setting Level III Neonatal Intensive Care Unit at a large teaching hospital in northeast China. Method Preterm infants (gestational age less than 37 weeks) ( n =80) were recruited and randomly assigned using a random table format to either an incubator group ( n =40) or Kangaroo Mother Care group ( n =40). Pain assessments were carried out during four routine heel stick procedures. For the first heel stick, preterm infants in each group received no intervention (routinely stayed in incubator). During the next three heel sticks, the infants in Kangaroo Mother Care group received heel sticks during Kangaroo Mother Care, while infants in the incubator group received heel sticks in incubator. The procedure of each heel stick included 3 phases: baseline, blood collection and recovery. Crying, grimacing and heart rate in response to pain were evaluated at each phase across four heel sticks by three trained independent observers who were blinded to the purpose of the study. Data were analyzed by analysis of variance (ANOVA), with repeated measures at different evaluation phases of heel stick. Results 75 preterm infants completed the protocol. Between-group comparison revealed that preterm infants' heart rate was significantly lower, and the duration of crying and facial grimacing were both significantly shorter in the Kangaroo Mother Care group ( n =38) than the incubator group ( n =37) from the blood collection phase to recovery phase during repeated heel sticks. No significant within-group difference was found in heart rate between the baseline phase and recovery phase through repeated heel sticks for Kangaroo Mother Care group. In contrast, the incubator group experienced significant within group differences in heart rate between baseline and recovery through repeated heel sticks. Conclusion The effect of repeated Kangaroo Mother Care analgesia remains stable in preterm infants over repeated painful procedures. Given the many invasive procedures that are part of clinical care in preterm infants and most mothers preferred to provide comfort for their infants during painful procedures, Kangaroo Mother Care may be a safe analgesic alternative in preterm infants in whom it is feasible.

Mammalian early embryonic development is controlled by a unique program of gene expression, and involves epigenetic reprogramming of histone modifications and DNA methylation. SET and MYND domain-containing protein 3 (SMYD3) is a histone H3 lysine 4 methyltransferase that plays important roles in transcription regulation. The expression of SMYD3 has been studied in some cancer cell lines. However, its expression in oocytes and embryos has not previously been reported. Here, we detected the SMYD3 mRNA and found that it was expressed throughout bovine oocyte in vitro maturation and early embryonic development. Microinjection of SMYD3 siRNA at germinal vesicle stage decreased the transcription level of NANOG, and blocked the development of in vitro fertilization embryos at 4-8 cell stage. Conversely, Microinjection of SMYD3 siRNA at pronuclear stage did not affect early embryonic development. Our findings suggest that SMYD3 regulates the expression of NANOG, and plays an essential role in bovine early embryonic development.

Background Sucrose combined with non-nutritive sucking provided better pain relief than sucrose or non-nutritive sucking alone in a single painful procedure. However, whether the combination of non-nutritive sucking with sucrose could obtain a significant difference in analgesic effect of the repeated procedural pain than any single intervention has not been established. Objective To compare the effect of non-nutritive sucking and sucrose alone and in combination of repeated procedural pain in preterm infants. Design Randomized controlled trial. Setting A level III neonatal intensive care unit of a university hospital in China. Method Preterm infants born before 37 weeks of gestation were randomly assigned to four groups: routine care group (routine comfort through gentle touch when infants cried; n = 21), non-nutritive sucking group (n = 22), sucrose group (0.2 ml/kg of 20%; n = 21), sucrose (0.2 ml/kg of 20%) plus non-nutritive sucking group (n = 22). Each preterm infant received three nonconsecutive routine heel sticks. Each heel stick included three phases: baseline (the last 1 min of the 30 min without stimuli), blood collection, recovery (1 min after blood collection). Three phases of 3 heel stick procedures were videotaped. Premature infant pain profile (PIPP) score, heart rate, oxygen saturation and percentage of crying time were assessed by five independent evaluators who were blinded to the purpose of the study at different phases across three heel sticks. Data were analyzed by analysis of variance, with repeated measures at different evaluation phases of heel stick. Results 86 preterm infants completed the protocol. During the blood collection and recovery phases, combination group, had lower PIPP score (4.4 ± 1.5; 3.0 ± 0.8), lower heart rate (138.6 ± 7.9; 137.4 ± 4.7), higher oxygen saturation (95.2 ± 1.6; 96.0 ± 1.2), and smaller percentage of crying time (11.5 ± 8.6; 4.6 ± 3.4), compared with the group has given non-nutritive sucking (9.3 ± 1.3, 6.8 ± 1.4; 154.2 ± 9.0, 148.0 ± 9.3; 92.9 ± 2.4, 94.1 ± 1.0; 44.2 ± 9.6, 31.2 ± 10.5; respectively) or sucrose (10.1 ± 2.0, 7.4 ± 1.6; 151.6 ± 9.6, 147.9 ± 6.9; 93.5 ± 1.7, 94.5 ± 1.2; 53.8 ± 16.7, 35.2 ± 13.9; respectively) or routine care (13.3 ± 1.6, 10.6 ± 1.9; 156.8 ± 7.2, 151.7 ± 7.9; 92.9 ± 2.1, 93.8 ± 1.6; 80.6 ± 7.6, 68.2 ± 9.9; respectively). Both non-nutritive sucking and sucrose were more effective in reducing preterm infants' PIPP score and percentage of crying time than routine care. There was no difference in PIPP score, heart rate, oxygen saturation and percentage of crying time between the non-nutritive sucking and sucrose groups. Conclusion The combination of non-nutritive sucking with sucrose provided better pain relief during repeated painful procedures than when non-nutritive sucking or sucrose was used alone. The effect of non-nutritive sucking was similar to that of sucrose on repeated procedural pain.

M-type (Kv7, KCNQ) potassium channels are proteins that control the excitability of neurons and muscle cells. Many physiological and pathological mechanisms of excitation operate via the suppression of M channel activity or expression. Conversely, pharmacological augmentation of M channel activity is a recognized strategy for the treatment of hyperexcitability disorders such as pain and epilepsy. However, physiological mechanisms resulting in M channel potentiation are rare. Here we report that intracellular free zinc directly and reversibly augments the activity of recombinant and native M channels. This effect is mechanistically distinct from the known redox-dependent KCNQ channel potentiation. Interestingly, the effect of zinc cannot be attributed to a single histidine- or cysteine-containing zinc-binding site within KCNQ channels. Instead, zinc dramatically reduces KCNQ channel dependence on its obligatory physiological activator, phosphatidylinositol 4,5-bisphosphate (PIP2). We hypothesize that zinc facilitates interactions of the lipid-facing interface of a KCNQ protein with the inner leaflet of the plasma membrane in a way similar to that promoted by PIP2. Because zinc is increasingly recognized as a ubiquitous intracellular second messenger, this discovery might represent a hitherto unknown native pathway of M channel modulation and provide a fresh strategy for the design of M channel activators for therapeutic purposes.

The Ca2+ activated Cl− channels (CaCCs) play a multitude of important physiological functions. A number of candidate proteins have been proposed to form CaCC, but only two families, the bestrophins and the TMEM16 proteins, recapitulate the properties of native CaCC in expression systems. Studies of endogenous CaCCs are hindered by the lack of specific pharmacology as most Cl− channel modulators lack selectivity and a systematic comparison of the effects of these modulators on TMEM16A and bestrophin is missing. In the present study, we studied seven Cl− channel inhibitors: niflumic acid (NFA), NPPB, flufenamic acid (FFA), DIDS, tannic acid, CaCCinh-A01 and T16Ainh-A01 for their effects on TMEM16A and bestrophin-1 (Best1) stably expressed in CHO (Chinese hamster ovary) cells using patch clamp technique. Among seven inhibitors studied, NFA showed highest selectivity for TMEM16A (IC50 of 7.40 ± 0.95 μM) over Best1 (IC50 of 102.19 ± 15.05 μM). In contrast, DIDS displayed a reverse selectivity inhibiting Best1 with IC50 of 3.93 ± 0.73 μM and TMEM16A with IC50 of 548.86 ± 25.57 μM. CaCCinh-A01 was the most efficacious blocker for both TMEM16A and Best1 channels. T16Ainh-A01 partially inhibited TMEM16A currents but had no effect on Best1 currents. Tannic acid, NPPB and FFA had variable intermediate effects. Potentiation of channel activity by some of these modulators and the effects on TMEM16A deactivation kinetics were also described. Characterization of Cl− channel modulators for their effects on TMEM16A and Best1 will facilitate future studies of native CaCCs.

A temperature- and photo-excitation-density-dependent electron spin dephasing process has been studied by time-resolved magneto-optical Kerr effect (TR-MOKE) measurements for heavily-doped (Ga,Mn)As after appropriate annealing treatment. Unlike the as-grown (Ga,Mn)As in which s-d scattering is dominant for spin dephasing at low temperature, the exchange scattering induced by Mn ions is efficiently suppressed after annealing. For annealed (Ga,Mn)As, the p-d exchange coupling proves to be important for the electron spin dephasing process. Moreover, the Coulomb scattering arising from the weakly-localized holes and Mn impurities is revealed to play an important role in the electron spin dephasing after annealing. Our results demonstrate that the impurityinduced disorder plays a significant role in the electron spin-dephasing process in (Ga,Mn)As when Mn is over doped by as much as 15%, which is a critical issue that needs to be considered to achieve high-quality (Ga,Mn)As thin films with a higher Curie temperature TC and better functionality.

The purpose of this study is to propose and test an integrative model of relational benefit and trustworthiness development process by conceptualizing that trustworthiness in electronic catalog markets is influenced by relational commitment and relational satisfaction. To capture the full picture of trustworthiness in electronic markets, relational benefit is divided into three main categories: trust benefit, economic benefit and social benefit. From 1762 obtained data, hypotheses are tested using structural equation modeling. The results show that the three categories influence trustworthiness from different angles. Trust benefit affects the trustworthiness with both relational loyalty and relational satisfaction. Economic benefit can affect the trustworthiness directly and indirectly with relational satisfaction and relational commitment. Social benefit does not affect the trustworthiness directly, but through relational satisfaction and relational commitment ultimately. Generally, trust benefit affects the trustworthiness most in electronic markets, economic benefit in the next place and social benefit influences least.

Single-crystalline Co 2 MnAl Heusler alloy film has been successfully grown on GaAs (001) substrate by molecular-beam epitaxy (MBE). The complex multistep magnetic switchings with single, double, and triple loops, deriving from the in-plane uniaxial magnetic anisotropy superimposed with a cubic anisotropy, have been observed experimentally. All switching processes are revealed to be mediated by the sweeping of 90° and 180° domain walls, and can be explained successfully based on the domain energetics. Theoretical calculation of hard axis orientation using free energy density shows excellent agreement with the experimental result.

Aims: Neuropeptide substance P (SP) is produced and released by a subset of peripheral sensory neurons that respond to tissue damage (nociceptors). SP exerts excitatory effects in the central nervous system, but peripheral SP actions are still poorly understood; therefore, here, we aimed at investigating these peripheral mechanisms. Results: SP acutely inhibited T-type voltage-gated Ca2+ channels in nociceptors. The effect was mediated by neurokinin 1 (NK1) receptor-induced stimulation of intracellular release of reactive oxygen species (ROS), as it can be prevented or reversed by the reducing agent dithiothreitol and mimicked by exogenous or endogenous ROS. This redox-mediated T-type Ca2+ channel inhibition operated through the modulation of CaV3.2 channel sensitivity to ambient zinc, as it can be prevented or reversed by zinc chelation and mimicked by exogenous zinc. Elimination of the zinc-binding site in CaV3.2 rendered the channel insensitive to SP-mediated inhibition. Importantly, peripherally applied SP significantly reduced bradykinin-induced nociception in rats in vivo; knock-down of CaV3.2 significantly reduced this anti-nociceptive effect. This atypical signaling cascade shared the initial steps with the SP-mediated augmentation of M-type K+ channels described earlier. Innovation: Our study established a mechanism underlying the peripheral anti-nociceptive effect of SP whereby this neuropeptide produces ROS-dependent inhibition of pro-algesic T-type Ca2+ current and concurrent enhancement of anti-algesic M-type K+ current. These findings will lead to a better understanding of mechanisms of endogenous analgesia. Conclusion: SP modulates T-type channel activity in nociceptors by a redox-dependent tuning of channel sensitivity to zinc; this novel modulatory pathway contributes to the peripheral anti-nociceptive effect of SP. Antioxid. Redox Signal. 25, 233–251.

KCNQ (Kv7) potassium voltage-gated channels are expressed in the dorsal root ganglion (DRG) sensory neurons where they play an important role in controlling DRG neuron excitability. Therefore, any substance modulating the activity of these channels could significantly affect the thresholds and firing rates of DRG neurons, including nociceptors. KCNQ channels are potently augmented by reactive oxygen species, therefore, here we investigated potential effects on KCNQ currents of two redox-related compounds, ascorbate and zinc. Potassium currents were measured in CHO cells overexpressing KCNQ4 subunit, using perforated patch clamp technique. Extracellular perfusion of ascorbate increases KCNQ4 currents by 1.96±0.27. This effect was completely reverted by DTT (0.90±0.29), but not by the Zn chelator TPEN. The removal of the redox-sensitive cysteine cluster in the S2-S3 linker (KCNQ4CCC156-158AAA) completely abolished the ascorbate effect. Application of extracellular ZnCl2 (1-100 μM) was without an effect on KCNQ4 currents while inclusion of 10 μM ZnCl2 in the pipette solution increased the KCNQ4 current amplitude from 536±135 pA to 927±177 pA. Extracellular perfusion of zinc ionophore zinc pyrithione (ZnPy) increased the intracellular concentration of Zinc, as shown with FluoZin3 imaging in HEK cells. Additionally, ZnPy increased the KCNQ4 currents by 2.40±0.40 fold, similarly ZnPy also significantly augmented KCNQ2/3 currents. This increase was completely reverted by TPEN (0.89±0.18) but not by DTT. The increase of KCNQ4 currents by ZnPy was identical between the wild-type and the KCNQ4CCC156-158AAA mutant channel. Taken together, these results suggest that both extracellular ascorbate and intracellular Zn can increase KCNQ currents via distinct mechanisms.

Background Although sucrose is most extensively examined for its analgesia effect on a single procedural pain, neonates in neonatal intensive care units can be exposed to numerous painful procedures every day requiring multiple doses of sucrose. Some experiments have been performed to examine the efficacy and safety of repeated sucrose administration for repeated procedural pain; however, a systematic review of this topic has not yet been carried out. Objective To identify and assess the evidence demonstrating the efficacy and safety of repeated sucrose for repeated procedural pain in neonates. Method A systematic review was conducted using the Cochrane methodology. Pubmed, Cochrane Library, Web of Science, CINAHL (Cumulative Index to Nursing and Allied Health Literature), CBMdisc, CNKI, VIP, and Wanfang databases were searched through December 2015. All related abstracts were reviewed and the full texts of relevant articles were studied. Randomized controlled trials (RCTs) were included. Risk of bias was assessed for RCTs using quality critical appraisal criteria recommended by Cochrane Handbook. A standardised data form was used to extract information. Results Eight RCTs met our inclusion criteria. Different study designs were used in the included RCTs, which did not allow us to carry out a meta-analysis. The findings from this review indicated that repeated sucrose was effective in reducing both behavioral pain response and composite pain scores during repeated procedural pain. However, as for physiological pain response, one trial found less variability in physiological pain response for term neonates in the sucrose group than the sterile water group, while two trials demonstrated repeated sucrose was inefficacious for preterm neonates. Regarding the clinical outcomes, no study reported adverse effects related to the repeated sucrose administration. Regarding the neurobehavioral development, two trials reported repeated sucrose for repeated procedural pain would not lead to poor neurologic development, while one trial reported that preterm infants 10 doses of sucrose per 24h in the first week of life had poorer neurologic development compared with infants who received fewer sucrose doses. What's more, no study reported the long-term neurobehavioral development outcome of neonates who repeatedly received sucrose across repeated procedural pain. Conclusion Evidence regarding the efficacy and safety of repeated sucrose across repeated procedural pain for neonates is limited. More prospective, multi-centered, large randomized controlled clinical trials with a standardised study design are required before sucrose can be recommended widely as an analgesia for repeated procedural pain in neonates.

In a previous study, we showed that membrane depolarization induced elevation of membrane phosphatidylinositol 4,5-bisphosphates (PtdIns(4,5)P(2), also known as PIP(2)) and subsequently increased the KCNQ2/Q3 currents expressed in Xenopus oocytes through increased PI4 kinase activity. In this study, the underlying mechanism for this depolarization-induced enhancement of PIP(2) synthesis was further investigated. Our results indicate that activation of protein kinase C (PKC) isozyme βII was responsible for the enhanced PIP(2) synthesis. We found that phorbol-12-myristate, 13-acetate (PMA), an activator of PKC, mimicked the effects of the membrane depolarization by increasing KCNQ2/Q3 activity, elevating membrane PIP(2) levels and increasing activity of PI4 kinase β. Furthermore, membrane depolarization enhanced PKC activity. The effects of both depolarization and PMA were blocked by a PKC inhibitor or PI4 kinase β RNA interference. Further results demonstrate that the depolarization selectively activated the PKC βII isoform and enhanced its interaction with PI4 kinase β. These results reveal that the depolarization-induced elevation of membrane PIP(2) is through activation of PKC and the subsequent increased activity of PI4 kinase β.

Transient memristors are prospective candidates for both secure memory systems and biointegrated electronics, which are capable to physically disappear at a programmed time with a triggered operation. However, the sneak current issue has been a considerable obstacle to achieve high-density transient crossbar array of memristors. To solve this problem, it is necessary to develop a transient switch device to turn the memory device on and off controllably. Here, a dissolvable and flexible threshold switching (TS) device with a vertically crossed structure is introduced, which exhibits a high selectivity of 107 , steep turn-on slope of

Development of a microsphere-based competitive fluorescence immunoassay for the determination of hazardous low-molecular-weight compounds in food is described. In this method, antigens are covalently bound to carboxy-modified microspheres to compete monoclonal antibody with low-molecular-weight compounds in food samples; mouse IgG/fluorescein isothiocyanate conjugate is used as the fluorescent molecular probe. Thus, the hazardous low-molecular-weight compounds are quantified using a multiparameter flow cytometer. This method has been evaluated using clenbuterol as a model compound. It has a sensitivity of 0.01 ng/mL with dynamic range of 0.01–100 ng/mL, and the concentration of clenbuterol providing 50% inhibition (IC 50 ) is 1.1 ng/mL. The main advantages of this method are its high efficiency, biocompatibility, and selectivity, as well as ultralow trace sample consumption and low cost.

Magneto-transport measurements have been carried out on double/single-barrier-doped In0.52Al0.48As/In0.53Ga0.47As/In0.52Al0.48As quantum well samples from 1.5 to 60 K in an applied magnetic field up to 13 T. Beating Shubnikov-de Haas oscillation is observed for the symmetrically double-barrier-doped sample and demonstrated due to a symmetric state and an antisymmetric state confined in two coupled self-consistent potential wells in the single quantum well. The energy separation between the symmetric and the antisymmetric states for the double-barrier-doped sample is extracted from experimental data, which is consistent with calculation. For the single-barrier-doped sample, only beating related to magneto-intersubband scattering shows up. The pesudospin property of the symmetrically double-barrier-doped single quantum well shows that it is a good candidate for fabricating quantum transistors. (c) 2007 Elsevier Ltd. All rights reserved.

With the aid of the acceptance ratio method, the depletion effects between two large hard spheres immersed in the sea of small spheres which is further confined in a small cylinder are studied by the Monte Carlo simulations. The numerical results show that the effects on both the depletion potentials and depletion forces from the geometrical confinement of the cylinder are stronger than that from two parallel plates. On the other hand, with the increase of the diameter of the cylinder or the decrease of the volume fraction, the depletion effects decrease.

Many studies have shown that natural dietary agents, in combination with chemical agents, can improve the therapeutic response of cancers to chemotherapy and reduce the associated side-effects. In the present study, we investigated the therapeutic potential and mechanisms of anticancer effects for the combination of 5-fluorouracil (5-FU) and resveratrol (Res). In these studies, we employed the cancer cell lines TE-1 and A431 and an animal model of skin cancer. The presented results provide the first evidence that Res can enhance the anti-tumor potency of 5-FU by inducing S-phase arrest. The combination of Res and 5-FU demonstrates synergistic efficacy, causing tumor regression in a two-stage model of mouse skin carcinogenesis induced by DMBA and TPA. There was clear evidence of Res augmenting the growth inhibitory effect of 5-FU on the TE-1 and A431 cancer cells in vitro. In the in vivo studies, the tumor regression rate in the combination group increased significantly after four weeks of treatment ( P

Precision measurement technology is the important measure of a nation's industrial technology level. However, with the rapid development of modern science and technology, metrological grating directly used for displacement measurement has could not meet the needs of contemporary people to the accuracy of measurement. So it is necessary to subdivide the grating sensor signal, especially the fine subdivision which has been increasingly concerned. Aiming at the constructor method used in the specific implementation process of the fine subdivision of the grating sensor signal, two schemes are put forward in this paper. Based on the analysis and comparison of the two methods, at last, the optimal design scheme will be determined.

KCNQ potassium channels which underlie neuronal M current play dominant roles in controlling neuronal excitability. Inhibition or genetic loss of M channels are implicated in many excitability disorders (e.g. epilepsy, pain, deafness, arrhythmia), while M channel openers retigabine and flupirtine are used clinically as anticonvulsant drugs and analgesics. Zinc pyrithione (ZnPy) is one of the recently discovered M channel openers which activity was previously attributed to the pyrithione moiety; ZnPy is also used as zinc ionophore. Here we show that the likely mechanism of ZnPy action on KCNQ channels is elevation of intracellular zinc which, in turn, activates the channels. Using patch-clamp recordings we show that 10μM ZnPy increased the recombinant KCNQ4 and KCNQ2/3 currents as well as native M current in DRG neurons by 2.4±0.4, 1.6±0.1 and 1.6±0.2 fold respectively; these effects were completely reversed by zinc chelator TPEN (20μM) added in the presence of ZnPy. Fluorescent zinc imaging with FluoZin3TM in HEK293 cells and DRG neurons demonstrated that ZnPy induced robust intracellular zinc rises which were completely reversed by TPEN. Four other chemically unrelated zinc ionophores PDTC, DEDTC, DIQ and Zinc ionophore I had similar to ZnPy effects: all four compounds augmented KCNQ4 and KCNQ2/3 currents and induced intracellular zinc rises; TPEN completely abolished these effects. Using voltage sensitive phosphatase CiVSP we found that the Ci-VSP-dependent PIP2 hydrolysis strongly inhibited recombinant KCNQ4 and KCNQ2/3, however, ZnPy and PDTC completely abolished these effect rendering channels insensitive to Ci-VSP activation. TIRF imaging using optical PIP2 reporter PLCδPH-GFP confirmed that neither ZnPy nor PDTC affected the ability of CiVSP to hydrolyze PIP2, as determined by the depolarization-induced PLCδPH-GFP translocation. In sum, our data suggest that intracellular zinc potently augment KCNQ channel activity by reducing channel requirement for PIP2.

Nitrides could create opportunities of tuning resistive-switching (RS) characteristics due to their different electrical properties and ionic chemistry with oxides. Here, we reported on the effect of nitrogen-accommodation ability of electrodes in SiNx-based RS devices. The Ti/SiNx/Pt devices show a self-compliance bipolar RS with excellent reliability. The W/SiNx/Pt devices provide an unstable RS and fall to an intermediate resistance state (IRS) after a set process. The low resistance states of the Ti/SiNx/Pt devices obey Ohmic conduction and Frenkel-Poole emission from a conductive channel. The IRS of the W/SiNx/Pt devices conforms to Schottky emission and Fowler-Nordheim tunneling from a conductive channel/insulator/electrode structure. A nitrogen-ion-based model is proposed to explain the experimental results. According to the model, the nitrogen-accommodation ability of the electrodes dominates the nitrogen-reservoir size and the nitrogen-ion migration at the metal/SiNx interface, modulating the RS ...

Complementary resistive switching (CRS) in single devices without internal electrodes is attractive in high-density memory applications because it simplifies fabrication and avoids the complicated controlling and matching needed when using two resistive switching (RS) devices, as in conventional CRS devices. To improve the performance of such devices, however, the CRS mechanism must be understood further. Here, the authors report on voltage-amplitude-controlled CRS and self-compliance opposite-polarity bipolar RS in Pt/HfO2/HfOx/Pt memory devices. In these devices, CRS showed an almost symmetrical current–voltage hysteresis loop. Both the set voltages and hopping conduction mechanism of the high resistance states in both the bipolar RS were consistent with those of the CRS. An excess current beyond Ohmic conduction appeared before the reset switching in the bipolar RS. To interpret the characteristics of the CRS and bipolar RS, the authors propose a slender conductive filament model. According to this mod...

A number of clinical trials have shown that a high loading dose of atorvastatin (Ator) within 24h before percutaneous coronary intervention (PCI) exerts protective effects on the cardiovascular system. However, the potential mechanisms regarding this rapid benefit of Ator remain elusive. Our study introduced three different ischaemia/reperfusion (I/R) models: I/R in vivo, I/R in vitro and oxygen-glucose deprivation/recovery (OGD/R) in primary neonatal rat cardiac myocytes to observe the protective effect of a single loading dose of Ator pre-treatment and further to explore the potential mechanisms of this protective effect with confocal laser scanning microscopy, flow cytometry, biochemical and morphology methods. We found that the pre-treatment of high-dose Ator decreased the cardiac injury and maintained the integrity of mitochondria in all three of the I/R models, which was similar to ischaemic pre-conditioning (IPC). We used the mitochondrial K(ATP) channels (mitoKATP channels) inhibitor 5-hydroxydecanoate (5-HD) and the mitochondrial permeability transition pore (mPTP) opener lonidamine (LND) to analyse the underlying mechanisms. The results showed that the pre-treatment of Ator significantly decreased I/R-induced injury, and maintained the functional integrity of mitochondria through alleviating Ca(2+) overload, reactive oxygen species burst, inhibiting the opening of mPTP and preventing mitochondrial membrane potential (ΔΨm) depolarisation. The present results demonstrated that a single dose of Ator might protect the myocardium from I/R-induced injury by inhibiting the mPTP opening through activating the mitoKATP channels. This result may contribute toward the development of novel strategies for clinical cardioprotection against I/R injury.

Epigenetic silencing of tumor-suppressor genes by promoter hypermethylation contributes considerably to the initiation and progression of cancer. Nucleoside analogs, the most widely used DNA methylation inhibitors, have the drawbacks of inducing repetitive sequence hypomethylation. Here, we aimed to specifically reverse tumor-suppressor gene (TSG) promoter hypermethylation with bovine oocyte extract. H460 human lung cancer cells were reversibly permeabilized and incubated with bovine oocyte extract for 3.5 h. The extract treatment led to significant demethylation of the hypermethylated promoters of the TSGs RUNX3, CDH1, RASSF1A and WIF1; however, the methylation levels of repetitive sequences were not affected. The promoter demethylation induced by bovine oocyte extract substantially upregulated the expression of RUNX3, CDH1, RASSF1A and WIF1, and significantly inhibited the anchorage-independent proliferation, migration and invasion of H460 cells. This study demonstrates that bovine oocyte extract can reverse the malignant phenotype by serving as an efficient and safe DNA demethylator. The active demethylation activity of bovine oocyte extract is valuable for dissecting the epigenetic alterations in cancer cells and developing novel safe anticancer drugs based on epigenetic mechanisms.

Our objective is to investigate the effect of valproic acid (VPA), a histone deacetylase inhibitor, on early embryonic development. We studied the effect of VPA on the in vitro maturation of bovine oocytes, and on the development of bovine embryos derived from in vitro fertilization (IVF) or parthenogenesis. Germinal vesicle stage bovine oocytes were cultured with different concentrations of VPA for 24 h; low dose VPA treatment (0.03 and 0.3 mM) had no effect on oocyte maturation, but 3 and 6 mM VPA significantly decreased maturation rate; when used for IVF or parthenogenesis, VPA-treated oocytes generated significantly lowered blastocyst rate. Oocytes matured in vitro were fertilized or underwent parthenogenetic activation; 6 h later, they were exposed to VPA for 48 h, and then the cleavage rate, blastocyst rate and mRNA expression levels of transcription factors (Oct4, Nanog, and Cdx2) were assessed. For embryos cultured in 0.3 mM VPA, there was no remarkable change in cleavage rate or blastocyst rate, but the expression of Oct4 and Nanog in blastocysts was significantly increased. For embryos treated with 3.0 mM VPA, the cleavage rate and blastocyst rate were significantly decreased. In conclusion, low dose VPA has no effect on oocyte maturation but affects subsequent embryonic development. Low dose VPA administration to IVF embryos had no effect on embryonic development, but the expression of several important transcription factors was increased. Treatment of IVF embryos with low dose VPA may improve their development potential.

Charge-trapping or ionic mechanisms of the resistive switching (RS) at metal/Nb-doped SrTiO3 (NSTO) interfaces are still unclear. Here, the electrical properties and RS evolution at Pt/NSTO interfaces are investigated. A volatile RS in the fresh junctions complies with Schottky theory involving an interfacial layer and electrically dependent permittivity. The RS is interpreted by a redox-reaction modulated barrier model. A nonvolatile RS emerges and evolves with increasing the forward voltage. I–V and C–V characteristics imply different conductive filament (CF) configurations in high and low resistance states. An in-barrier ionic CF model is established for the nonvolatile RS. The coherent ionic models are beneficial for understanding the interfacial role in RS and for regulating RS characteristics or realizing high quality metal/oxide diodes.

In this letter, dissolvable and biodegradable resistive switching devices with a cell structure of Mg/MgO/Mg were demonstrated. Electrical tests demonstrated good memory characteristics for nonvolatile application. The dissolution rate of Mg and MgO is characterized in deionized (DI) water and in phosphate-buffered saline solution, with clear difference, 0.36, 1.25, 0.057, and 0.13 nm/s, respectively. The Mg/MgO/Mg devices on silk fibroin substrates are able to be completely dissolved as fast as 30 min while immersed in DI water. The Mg/MgO/Mg devices have excellent prospects for the applications in transient electronics, secure memory systems, and implantable medical therapy devices.

BACKGROUND AND PURPOSE: Celecoxib (CXB) is a widely prescribed COX-2 inhibitor used clinically to treat pain and inflammation. Recently, COX-2 independent mechanisms have been described to be the targets of CXB. For instance, ion channels such as the voltage-gated sodium channel, L-type calcium channel, Kv2.1, Kv1.5, Kv4.3 and HERG potassium channel were all reported to be inhibited by CXB. Our recent study revealed that CXB is a potent activator of Kv7/M channels. M currents expressed in dorsal root ganglia play an important role in nociception. Our study was aimed at establishing the role of COX-2 independent M current activation in the analgesic action of CXB. METHODS AND RESULTS: We compared the effects of CXB and its two structural analogues, unmethylated CXB (UMC) and 2,5-dimethyl-CXB (DMC), on Kv7/M currents and pain behavior in animal models. UMC is a more potent inhibitor of COX-2 than CXB while DMC has no COX-2 inhibiting activity. We found that CXB, UMC and DMC concentration-dependently activated Kv7.2/7.3 channels expressed in HEK293 cells and the M-type current in dorsal root ganglia neurons, negatively shifted I-V curve of Kv7.2/7.3 channels, with a potency and efficiency inverse to their COX-2 inhibitory potential. Furthermore, CXB, UMC and DMC greatly reduced inflammatory pain behavior induced by bradykinin, mechanical pain behavior induced by stimulation with von Frey filaments and thermal pain behavior in the Hargreaves test. CXB and DMC also significantly attenuated hyperalgesia in chronic constriction injury neuropathic pain. CONCLUSION: CXB, DMC and UMC are openers of Kv7/M K(+) channels with effects independent of COX-2 inhibition. The analgesic effects of CXBs on pain behaviors, especially those of DMC, suggest that activation of Kv7/M K(+) channels may play an important role in the analgesic action of CXB. This study strengthens the notion that Kv7/M K(+) channels are a potential target for pain treatment.

Ion channels involved in the migration of tumor cells that is required for their invasion and metastasis. In this paper, we describe the interaction of TRPM7 channel and epidermal growth factor (EGF), an important player in cancer development in the migration of lung cancer cells. The TRPM7 currents in A549 cells were first characterized by means of electrophysiology, pharmacology and RNA interference. Removing Ca2+ from the extracellular solution not only potentiated a large inward current, but also abolished the outward rectification. 200 μM 2-APB inhibited the outward and the inward TRPM7 currents and at the same time restored the property of outward rectification. EGF greatly enhanced the migration of A549 cells, and also markedly up-regulated the membrane protein expression of TRPM7 and the amplitude of TRPM7 currents. Depressing the function of TRPM7 with RNA interference or pharmacological agents not only reversed the EGF-enhanced migration of A549 cells but also inhibited the basal migration of A549 cells in the absence of EGF. Thus it seems that TRPM7 plays a pivotal role in the migration of A549 cells induced by EGF and thus could be a potential therapeutic target in lung cancers.

In this study we developed zinc chloride activation method to prepare activated carbon (AC) from the stick woods of one-year-old Eucommia Ulmoides Oliv cultivated from leaf-oriented tree model We determined the effect of zinc chloride (ZnCl 2 ) concentration, mass ratio of solvent to material, dip time, activation temperature and activation time on the absorption capacity of the absorbent. The results showed that the optimal condition for preparation of AC was 35% of ZnCl 2 , 4.0 ∶ 1 mass ratio of solvent to material, 15h of dip time, 600 °C of activation temperature and 180 min of activation time. Under the optimal condition, the yield of the AC was 32.5 %, with iodine absorption of 1210.8 mg/g and methylene blue absorption of 216.5 mg/g, which met the requirement of the first grade product standard of GB/T13803.2-1999.

In today's fiercely competitive environment, retaining customers is a challenge. Perceived risk is frequently an important effecting factor in consumer purchasing process. So service strategy before sale, during sale and after sale is the same important. A clear service strategy will include strategies with different pivot and content to reduce a customer's perceived risk.

Based on immunoassay, we developed a method to detect Potato Virus A (PVA) using one-step cytometric bead array (CBA).Using fluorescent beads as carriers, we formed the complexes of bead-capture antibody-PVA-fluoresceinisothiocyanate (FITC) labeled detection antibody by immunoreaction of double antibody sandwich on bead surface. We measured the fluorescent signals produced from beads and from FITC with a multiparameter flow cytometer.By optimization test, capture antibody and detection antibody (from PVA detection kit, Agdia, USA) were finally diluted at 1:50 (4 ug/mL) and 1:25 to be used in one step CBA, respectively. A total CBA reaction time of 2 h was needed. No cross reactivity with other plant virus similar to potato virus Y, lettuce mosaic virus and tomato ring spot virus were found. Detection sensitivity for positive control sample in one-step CBA was 4 folds higher than that in normal plate double antibodies sandwich enzyme-linked immunosorbent assay (DAS-ELISA).A one-step CBA method for rapid and sensitive detection of PVA is developed.

Consumer often weighs perceived benefit against perceived risk when making purchase decision. Most former studies pay attention to increasing consumer's perceived benefit. The study concerning reducing perceived risk is very lacking. Identifying and facing perceived risk is an important approach to break down buying resistance. The study brings forward a suit of method and process explore components of perceived risk.

This paper proposes a practical comprehensive hierarchy and method for urban distribution system evaluation on the basis of modern systematic and quantitative comprehensive evaluation theories. First, analytic hierarchy process (AHP) is combined with Delphi to establish the hierarchy; next, by means of fuzzy membership function, the scoring standard system is constructed; then, traditional problem analysis method is improved by a comprehensive one. The result contains overall and individual indices, e.g. substations and feeders with most problems are listed. Software has been already implemented in Beijing Electric Power Corporation, China. Through an interface with AM/FM/GIS, engineers can use this system to perform overall evaluation conveniently. (7 pages)