Disjoining Pressure of Water in Nanochannels.

The disjoining pressure of water was estimated from wicking experiments in 1D silicon dioxide nanochannels of heights of 59, 87, 124, and 1015 nm. The disjoining pressure was found to be as high as ∼1.5 MPa while exponentially decreasing with increasing channel height. Such a relation resulting from the curve fitting of experimentally derived data was implemented and validated in computational fluid dynamics. The implementation was then used to simulate bubble nucleation in a water-filled 59 nm nanochannel to determine the nucleation temperature. Simultaneously, experiments were conducted by nucleating a bubble in a similar 58 nm nanochannel by laser heating. The measured nucleation temperature was found to be in excellent agreement with the simulation, thus independently validating the disjoining pressure relation developed in this work. The methodology implemented here integrates experimental nanoscale physics into continuum simulations thus enabling numerical study of various phenomena where disjoining pressure plays an important role.

Disruption of hepatic small heterodimer partner induces dissociation of steatosis and inflammation in experimental nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease worldwide and is characterized by steatosis, inflammation, and fibrosis. The molecular mechanisms underlying NASH development remain obscure. The nuclear receptor small heterodimer partner (Shp) plays a complex role in lipid metabolism and inflammation. Here, we sought to determine SHP's role in regulating steatosis and inflammation in NASH. Shp deletion in murine hepatocytes (ShpHep-/-) resulted in massive infiltration of macrophages and CD4+ T cells in the liver. ShpHep-/- mice developed reduced steatosis, but surprisingly increased hepatic inflammation and fibrosis after being fed a high-fat, -cholesterol, and -fructose (HFCF) diet. RNA-Seq analysis revealed that pathways involved in inflammation and fibrosis are significantly activated in the liver of ShpHep-/- mice fed a chow diet. After having been fed the HFCF diet, WT mice displayed up-regulated peroxisome proliferator-activated receptor γ (Pparg) signaling in the liver; however, this response was completely abolished in the ShpHep-/- mice. In contrast, livers of ShpHep-/- mice had consistent NF-κB activation. To further characterize the role of Shp specifically in the transition of steatosis to NASH, mice were fed the HFCF diet for 4 weeks, followed by Shp deletion. Surprisingly, Shp deletion after steatosis development exacerbated hepatic inflammation and fibrosis without affecting liver steatosis. Together, our results indicate that, depending on NASH stage, hepatic Shp plays an opposing role in steatosis and inflammation. Mechanistically, Shp deletion in hepatocytes activated NF-κB and impaired Pparg activation, leading to the dissociation of steatosis, inflammation, and fibrosis in NASH development.

Inhibition of Nav1.7 channel by a novel blocker QLS-81 for alleviation of neuropathic pain.

Voltage-gated sodium channel Nav1.7 robustly expressed in peripheral nociceptive neurons has been considered as a therapeutic target for chronic pain, but there is no selective Nav1.7 inhibitor available for therapy of chronic pain. Ralfinamide has shown anti-nociceptive activity in animal models of inflammatory and neuropathic pain and is currently under phase III clinical trial for neuropathic pain. Based on ralfinamide, a novel small molecule (S)-2-((3-(4-((2-fluorobenzyl) oxy) phenyl) propyl) amino) propanamide (QLS-81) was synthesized. Here, we report the electrophysiological and pharmacodynamic characterization of QLS-81 as a Nav1.7 channel inhibitor with promising anti-nociceptive activity. In whole-cell recordings of HEK293 cells stably expressing Nav1.7, QLS-81 (IC50 at 3.5 ± 1.5 µM) was ten-fold more potent than its parent compound ralfinamide (37.1 ± 2.9 µM) in inhibiting Nav1.7 current. QLS-81 inhibition on Nav1.7 current was use-dependent. Application of QLS-81 (10 µM) caused a hyperpolarizing shift of the fast and slow inactivation of Nav1.7 channel about 7.9 mV and 26.6 mV, respectively, and also slowed down the channel fast and slow inactivation recovery. In dissociated mouse DRG neurons, QLS-81 (10 µM) inhibited native Nav current and suppressed depolarizing current pulse-elicited neuronal firing. Administration of QLS-81 (2, 5, 10 mg· kg-1· d-1, i.p.) in mice for 10 days dose-dependently alleviated spinal nerve injury-induced neuropathic pain and formalin-induced inflammatory pain. In addition, QLS-81 (10 µM) did not significantly affect ECG in guinea pig heart ex vivo; and administration of QLS-81 (10, 20 mg/kg, i.p.) in mice had no significant effect on spontaneous locomotor activity. Taken together, our results demonstrate that QLS-81, as a novel Nav1.7 inhibitor, is efficacious on chronic pain in mice, and it may hold developmental potential for pain therapy.

Evaporation Dynamics in Buried Nanochannels with Micropores.

Cross-connected buried nanochannels of height ∼728 nm, with micropores of ∼2 µm diameter present at each intersection, are used in this work to numerically and experimentally study droplet-coupled evaporation dynamics at room temperature. The uniformly structured channels/pores, along with their well-defined porosity, allow for computational fluid dynamics simulations and experiments to be performed on the same geometry of samples. A water droplet is placed on top of the sample causing water to wick into the nanochannels through the micropores. After advancing, the meniscus front stabilizes when evaporation flux is balanced with the wicking flux, and it recedes once the water droplet is completely wicked in. Evaporation flux at the meniscus interface of channels/pores is estimated over time, while the flux at the water droplet interface is found to be negligible. When the meniscus recedes in the channels, local contact line regions are found to form underneath the pores, thus rapidly enhancing evaporation flux as a power-law function of time. Temporal variation of wicking flux velocity and pressure gradient in the nanochannels is also independently computed, from which the viscous resistance variation is estimated and compared to the theoretical prediction.

Hepatocyte nuclear receptor SHP suppresses inflammation and fibrosis in a mouse model of nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem worldwide, ranging from nonalcoholic fatty liver (NAFL, steatosis without hepatocellular injury) to the more aggressive nonalcoholic steatohepatitis (NASH, steatosis with ballooning, inflammation, or fibrosis). Although many studies have greatly contributed to the elucidation of NAFLD pathogenesis, the disease progression from NAFL to NASH remains incompletely understood. Nuclear receptor small heterodimer partner (Nr0b2, SHP) is a transcriptional regulator critical for the regulation of bile acid, glucose, and lipid metabolism. Here, we show that SHP levels are decreased in the livers of patients with NASH and in diet-induced mouse NASH. Exposing primary mouse hepatocytes to palmitic acid and lipopolysaccharide in vitro, we demonstrated that the suppression of Shp expression in hepatocytes is due to c-Jun N-terminal kinase (JNK) activation, which stimulates c-Jun-mediated transcriptional repression of Shp Interestingly, in vivo induction of hepatocyte-specific SHP in steatotic mouse liver ameliorated NASH progression by attenuating liver inflammation and fibrosis, but not steatosis. Moreover, a key mechanism linking the anti-inflammatory role of hepatocyte-specific SHP expression to inflammation involved SHP-induced suppression of NF-κB p65-mediated induction of chemokine (C-C motif) ligand 2 (CCL2), which activates macrophage proinflammatory polarization and migration. In summary, our results indicate that a JNK/SHP/NF-κB/CCL2 regulatory network controls communications between hepatocytes and macrophages and contributes to the disease progression from NAFL to NASH. Our findings may benefit the development of new management or prevention strategies for NASH.

Pool Boiling Coupled with Nanoscale Evaporation Using Buried Nanochannels.

Pool boiling is explicitly coupled with nanoscale evaporation by using buried nanochannels of height ∼728 nm and ∼100 nm to enhance critical heat flux (CHF) by ∼105%. Additional menisci and contact line formation in nanochannels are found to be the dominant factors of CHF enhancement. Wicking assists in creating the additional contact line but does not serve as the primary measurable factor in predicting such enhancement based on CFD simulations and wicking experiments. This work provides clarity on the roles of contact line and wicking in boiling heat transfer.

CXCL1 Derived from Mammary Fibroblasts Promotes Progression of Mammary Lesions to Invasive Carcinoma through CXCR2 Dependent Mechanisms.

With improved screening methods, the numbers of abnormal breast lesions diagnosed in women have been increasing over time. However, it remains unclear whether these breast lesions will develop into invasive cancers. To more effectively predict the outcome of breast lesions and determine a more appropriate course of treatment, it is important to understand the underlying mechanisms that regulate progression of non-invasive lesions to invasive breast cancers. A hallmark of invasive breast cancers is the accumulation of fibroblasts. Fibroblast proliferation and activation in the mammary gland is in part regulated by the Transforming Growth Factor beta1 pathway (TGF-ß). In animal models, TGF-ß suppression of CCL2 and CXCL1 chemokine expression is associated with metastatic progression of mammary carcinomas. Here, we show that transgenic overexpression of the Polyoma middle T viral antigen in the mouse mammary gland of C57BL/6 mice results in slow growing non-invasive lesions that progress to invasive carcinomas in a stage dependent manner. Invasive carcinomas are associated with accumulation of fibroblasts that show decreased TGF-ß expression and high levels of CXCL1, but not CCL2. Using co-transplant models, we show that decreased TGF-ß signaling in fibroblasts contribute to mammary carcinoma progression through enhancement of CXCL1/CXCR2 dependent mechanisms. Using cell culture models, we show that CXCL1 mediated mammary carcinoma cell invasion through NF-κB, AKT, Stat3 and p42/44MAPK dependent mechanisms. These studies provide novel mechanistic insight into the progression of pre-invasive lesions and identify new stromal biomarkers, with important prognostic implications.

Early Evaporation of Microlayer for Boiling Heat Transfer Enhancement.

For over five decades, an enhancement in pool boiling heat transfer has been achieved by altering the surface wetting, wickability, roughness, nucleation site density, and providing separate liquid/vapor pathways. In this work, a new enhancement mechanism based on the early evaporation of the microlayer is discovered and validated. The microlayer is a thin liquid film present at the base of a vapor bubble. The presence of microridges on the silicon dioxide surface partitions the microlayer and disconnects it from the bulk liquid, causing it to evaporate sooner, thus leading to increase in the bubble growth rate, heat transfer, departure frequency, and critical heat flux (CHF). Compared to a plain surface, an ∼120% enhancement in CHF is obtained with only an ∼18% increase in surface area. A CHF enhancement map is developed on the basis of the ridge height and spacing, resulting in three regions of full, partial, and no enhancement. The new mechanism is validated by comparing the growth rate of a laser-created vapor bubble on a ridge-structured surface and a plain surface, and the corresponding prediction of the CHF enhancement is found to be in good agreement with the experimental boiling data. This discovery opens up a new field of CHF enhancement and can potentially be coupled with existing techniques to further push the limits of boiling heat transfer.

Elevated CXCL1 expression in breast cancer stroma predicts poor prognosis and is inversely associated with expression of TGF-ß signaling proteins.

BACKGROUND: CXCL1 is a chemotactic cytokine shown to regulate breast cancer progression and chemo-resistance. However, the prognostic significance of CXCL1 expression in breast cancer has not been fully characterized. Fibroblasts are important cellular components of the breast tumor microenvironment, and recent studies indicate that this cell type is a potential source of CXCL1 expression in breast tumors. The goal of this study was to further characterize the expression patterns of CXCL1 in breast cancer stroma, determine the prognostic significance of stromal CXCL1 expression, and identify factors affecting stromal CXCL1 expression. METHODS: Stromal CXCL1 protein expression was analyzed in 54 normal and 83 breast carcinomas by immunohistochemistry staining. RNA expression of CXCL1 in breast cancer stroma was analyzed through data mining in http://www.Oncomine.org. The relationships between CXCL1 expression and prognostic factors were analyzed by univariate analysis. Co-immunofluorescence staining for CXCL1, α-Smooth Muscle Actin (α-SMA) and Fibroblast Specific Protein 1 (FSP1) expression was performed to analyze expression of CXCL1 in fibroblasts. By candidate profiling, the TGF-ß signaling pathway was identified as a regulator of CXCL1 expression in fibroblasts. Expression of TGF-ß and SMAD gene products were analyzed by immunohistochemistry and data mining analysis. The relationships between stromal CXCL1 and TGF-ß signaling components were analyzed by univariate analysis. Carcinoma associated fibroblasts isolated from MMTV-PyVmT mammary tumors were treated with recombinant TGF-ß and analyzed for CXCL1 promoter activity by luciferase assay, and protein secretion by ELISA. RESULTS: Elevated CXCL1 expression in breast cancer stroma correlated with tumor grade, disease recurrence and decreased patient survival. By co-immunofluorescence staining, CXCL1 expression overlapped with expression of α-SMA and FSP1 proteins. Expression of stromal CXCL1 protein expression inversely correlated with expression of TGF-ß signaling components. Treatment of fibroblasts with TGF-ß suppressed CXCL1 secretion and promoter activity. CONCLUSIONS: Increased CXCL1 expression in breast cancer stroma correlates with poor patient prognosis. Furthermore, CXCL1 expression is localized to α-SMA and FSP1 positive fibroblasts, and is negatively regulated by TGF-ß signaling. These studies indicate that decreased TGF-ß signaling in carcinoma associated fibroblasts enhances CXCL1 expression in fibroblasts, which could contribute to breast cancer progression.

[Mechanism of gold solid extraction from aurocyanide solution using D3520 resin impregnated with TRPO].

Trialkyphosphine oxides (TRPO) was successfully used for the impregnation of D3520 resin to prepare an extractant-impregnated resin (EIR). Solid extraction of Au(I) from alkaline cyanide solution was studied using this extractant-impregnated resin (EIR), with addition of cetyltrimethylammonium bromide (CTMAB), directly into the aurous aqueous phase in advance. The mechanism of solid extraction was further investigated by means of FTIR, XPS and SEM. The column separation studies have shown that cationic surfactant CTMAB played a key role in the solid phase extraction, and the resin containing TRPO were effective for the extraction of gold when the molar ratio of CTMAB: Au( I ) reached 1:1. FTIR spectroscopy of gold loaded EIR showed that the frequency of C[triple bond]N stretching vibration was at 2144 cm(-1), and the frequency of P=O stretching vibration shifted to lower frequency from 1153 to 1150 cm(-1). The XPS spectrum of N(1s), Au(4f7/2) and Au(4f5/2) sugges- ted that the coordination environment of gold did not change before and after extraction, and gold was still as the form of Au (CN)2(-) anion exiting in the loaded resin; O(1s) spectrum showed that the chemically combined water significantly increased after solid extraction from 30.74% to 42.34%; Comparing to the P(2p) spectrum before and after extraction, the binding energy increased from 132. 15 to 132. 45 eV, indicating there maybe existing hydrogen-bond interaction between P=O and water molecule, such as P=O...H-O-H. The above results obtained established that in the solid extraction process, the hydrophobic ion association [CTMA+ x Au(CN)] diffused from the bulk solution into the pores of the EIR, and then be solvated by TRPO adsorbed in the pores through hydrogen bonding bridged by the water molecules.

CCL2/CCR2 chemokine signaling coordinates survival and motility of breast cancer cells through Smad3 protein- and p42/44 mitogen-activated protein kinase (MAPK)-dependent mechanisms.

Increased cell motility and survival are important hallmarks of metastatic tumor cells. However, the mechanisms that regulate the interplay between these cellular processes remain poorly understood. In these studies, we demonstrate that CCL2, a chemokine well known for regulating immune cell migration, plays an important role in signaling to breast cancer cells. We report that in a panel of mouse and human breast cancer cell lines CCL2 enhanced cell migration and survival associated with increased phosphorylation of Smad3 and p42/44MAPK proteins. The G protein-coupled receptor CCR2 was found to be elevated in breast cancers, correlating with CCL2 expression. RNA interference of CCR2 expression in breast cancer cells significantly inhibited CCL2-induced migration, survival, and phosphorylation of Smad3 and p42/44MAPK proteins. Disruption of Smad3 expression in mammary carcinoma cells blocked CCL2-induced cell survival and migration and partially reduced p42/44MAPK phosphorylation. Ablation of MAPK phosphorylation in Smad3-deficient cells with the MEK inhibitor U0126 further reduced cell survival but not migration. These data indicate that Smad3 signaling through MEK-p42/44MAPK regulates CCL2-induced cell motility and survival, whereas CCL2 induction of MEK-p42/44MAPK signaling independent of Smad3 functions as an alternative mechanism for cell survival. Furthermore, we show that CCL2-induced Smad3 signaling through MEK-p42/44MAPK regulates expression and activity of Rho GTPase to mediate CCL2-induced breast cancer cell motility and survival. With these studies, we characterize an important role for CCL2/CCR2 chemokine signaling in regulating the intrinsic relationships between breast cancer cell motility and survival with implications on the metastatic process.

Dropwise Condensation in Ambient on a Depleted Lubricant-Infused Surface.

Durability of a lubricant-infused surface (LIS) is critical for heat transfer, especially in condensation-based applications. Although LIS promotes dropwise condensation, each departing droplet condensate acts as a lubricant-depleting agent due to the formation of wetting ridge and cloaking layer around the condensate, thus gradually leading to drop pinning on the underlying rough topography. Condensation heat transfer further deteriorates in the presence of non-condensable gases (NCGs) requiring special experimental arrangements to eliminate NCGs due to a decrease in the availability of nucleation sites. To address these issues while simultaneously improving heat-transfer performance of LIS in condensation-based systems, we report fabrication of both fresh LIS and a lubricant-depleted LIS using silicon porous nanochannel wicks as an underlying substrate. Strong capillarity in the nanochannels helps retain silicone oil (polydimethylsiloxane) on the surface even after it is severely depleted under tap water. The effect of oil viscosity was investigated for drop mobility and condensation heat transfer under ambient conditions, i.e., in the presence of NCGs. While fresh LIS prepared using 5 cSt silicone oil exhibited a low roll-off angle (∼1°) and excellent water drop (5 µL) sliding velocity ∼66 mm s-1, it underwent rapid depletion as compared to higher viscosity oils. Condensation performed on depleted nanochannel LIS with higher viscosity oil (50 cSt) resulted in a heat-transfer coefficient (HTC) of ∼2.33 kW m-2 K-1, which is a ∼162% improvement over flat Si-LIS (50 cSt). Such LIS promote fast drop shedding as is evident from the little change in the fraction of drops with diameter <500 µm from ∼98% to only ∼93% after 4 h of condensation. Improvement in HTC was also seen in condensation experiments conducted for 3 days where a steady HTC of ∼1.46 kW m-2 K-1 was achieved over the last 2 days. The ability of reported LIS to maintain long-term hydrophobicity and dropwise condensation will aid in designing condensation-based systems with improved heat-transfer performance.

Practical Predefined-Time Output-Feedback Consensus Tracking Control for Multiagent Systems.

This article addresses the issue of output-feedback consensus control of multiagent systems under the directed topology and subject to bounded external disturbances. By employing a smooth time-varying function, a distributed practical predefined-time (PPT) observer is developed to estimate the reference trajectory for the entire team (i.e., the leader's state) and a practical preset-time extended-state observer is also proposed to estimate bounded disturbances and unmeasurable system states. Next, a novel continuous and nonsingular PPT consensus control law is designed on the basis of the observers. Furthermore, the designed control protocol can achieve PPT stability, that is, consensus tracking errors are enforced to a neighborhood around zero within a predetermined time, which can be specified a priori, independent of initial states of agents and/or any other design parameters. Finally, illustrative numerical examples, including a comparative one, are provided to demonstrate the performance of the present predefined-time control approach.

Disjoining pressure driven transpiration of water in a simulated tree.

HYPOTHESIS: Transpiration occurs in 100 m tall redwood trees where water is passively pulled against gravity requiring the evaporating liquid meniscus in stomata pores to be under absolute negative pressures of -10 atm or higher. Disjoining pressure can significantly reduce pressure at meniscus in nanopores due to strong surface-liquid molecular interaction. Hence, disjoining pressure should be able to solely govern the transpiration process. SIMULATIONS: Expression of disjoining pressure in a water film is first developed from prior experimental findings. The expression is then implemented in a commercial CFD solver and validated against experimental data for water wicking in nanochannels of height varying from 59 nm to 1 µm. Following the implementation, the transpiration process is simulated in a 3D domain comprising of a nanopore connected to a tube with ground-based water tank, thus mimicking the stomata-xylem-soil pathway in a 100 m tall tree. FINDINGS: Disjoining pressure is found to induce absolute negative pressures as high as -23.5 atm at the evaporating meniscus and can also sustain high evaporation fluxes in nanopore before the meniscus completely dewets. This is the first report to integrate disjoining pressure into continuum simulations and study the transpiration process in a 100 m tall tree using such simulations.

Droplet Evaporation on Porous Nanochannels for High Heat Flux Dissipation.

Droplet wicking and evaporation in porous nanochannels is experimentally studied on a heated surface at temperatures ranging from 35 to 90 °C. The fabricated geometry consists of cross-connected nanochannels of height 728 nm with micropores of diameter 2 µm present at every channel intersection; the pores allow water from a droplet placed on the top surface to wick into the channels. Droplet volume is also varied, and a total of 16 experimental cases are conducted. Wicking characteristics such as wicked distance, capillary pressure, viscous resistance, and propagation coefficients are obtained at all surface temperatures. Evaporation flux from the nanochannels/micropores is estimated from the droplet experiments but is also independently confirmed via a new set of experiments where water is continuously fed to the sample through a microtube so that it matches the evaporation rate. Heat flux as high as ∼294 W/cm2 is achieved from channels and pores. The experimental findings are applied to evaluate the use of porous nanochannel geometry in spray cooling application and is found to be capable of passively dissipating high heat fluxes upto ∼77 W/cm2 at temperatures below nucleation, thus highlighting the thermal management potential of the fabricated geometry.

Fangchinoline induced G1/S arrest by modulating expression of p27, PCNA, and cyclin D in human prostate carcinoma cancer PC3 cells and tumor xenograft.

Prostate cancer (PCA) is the most common invasive malignancy and the second leading cause of cancer-related death in males. The present study investigated the effects of fangchinoline (Fan), an important compound in Stephania Tetradra S. Moore (Fenfangji) with pain-relieving, blood pressure-depressing, and antibiotic activities, on human PCA. It was found that Fan inhibited human prostate cancer cell lines (PC3) cell proliferation in a dose- and time-dependent manner. Studies of cell-cycle progression showed that the anti-proliferative effect of Fan was associated with an increase in the G1/S phase of PC3 cells. Western blot results indicated that Fan-induced G1/S phase arrest was mediated through inhibition of cyclin-regulated signaling pathways. Fan induced p27 expression and inhibited cyclin D and proliferating cell nuclear antigen (PCNA) expression in PC3 cells. Increased exposure time to Fan caused apoptosis of PC3 cells, which was associated with up-regulation of pro-apoptotic proteins Bax and caspase 3, and down-regulation of anti-apoptotic protein Bcl-2. Furthermore, Fan had anti-tumorigenic activity in vivo, including reduction of tumor volume and pro-apoptotic and anti-proliferative effects in a PC3 nude mouse xenograft. Taking all this together, it can be concluded that Fan is an effective anti-proliferative agent that modulates cell growth regulators in prostate cancer cells.

Transpiration Mechanism in Confined Nanopores.

In this work, molecular dynamics simulations show that liquid in a nanopore can be at thermodynamically stable high pressure even when connected to conventional bulk liquid. Such high pressure is associated with strong surface-liquid interaction. Evaporation of liquid in the pore creates a flow from the low pressure (bulk) region to the high pressure (nanopore) region. Such a counterintuitive flow occurs due to pressure being reduced in the pore from its thermodynamically stable state. The transition from high pressures to negative pressures in thin liquid films is also studied. This work provides insight into a possible mechanism of passive liquid transport in tall trees such as redwoods.

Quality assessment of tandem mass spectra using support vector machine (SVM).

BACKGROUND: Tandem mass spectrometry has become particularly useful for the rapid identification and characterization of protein components of complex biological mixtures. Powerful database search methods have been developed for the peptide identification, such as SEQUEST and MASCOT, which are implemented by comparing the mass spectra obtained from unknown proteins or peptides with theoretically predicted spectra derived from protein databases. However, the majority of spectra generated from a mass spectrometry experiment are of too poor quality to be interpreted while some of spectra with high quality cannot be interpreted by one method but perhaps by others. Hence a filtering algorithm that removes those spectra with poor quality prior to the database search is appealing. RESULTS: This paper proposes a support vector machine (SVM) based approach to assess the quality of tandem mass spectra. Each mass spectrum is mapping into the 16 proposed features to describe its quality. Based the results from SEQUEST, four SVM classifiers with the input of the 16 features are trained and tested on ISB data and TOV data, respectively. The superior performance of the proposed SVM classifiers is illustrated both by the comparison with the existing classifiers and by the validation in terms of MASCOT search results. CONCLUSION: The proposed method can be employed to effectively remove the poor quality spectra before the spectral searching, and also to find the more peptides or post-translational peptides from spectra with high quality using different search engines or de novo method.

Quercetin activates human Kv1.5 channels by a residue I502 in the S6 segment.

1. The aims of the present study were to investigate the pharmacological effects of quercetin on wild-type (WT) and mutant (I502A) human (h) Kv1.5 channel currents (I(kur)) and to identify whether mutation in the S6 segment is critical to activation of I(kur) by quercetin. 2. Experiments were performed on WT and site-directed mutant hKv1.5 channels, which were stably expressed in Xenopus oocytes using the two-microelectrode voltage-clamp technique. 3. Quercetin increased WT hKv1.5 channel current in a concentration-, voltage- and time-dependent manner, with an EC(50) of 37.8 micromol/L and a negative shift in the steady state activation and inactivation curves. Quercetin accelerated channel activation and inactivation, significantly decreasing activation and inactivation time constants. However, mutating the I502 residue to Ala abolished the activating effect of quercetin. Quercetin did not modify the activation and inactivation kinetics of I502A channels. As an anti-oxidant, tanshinone IIA (4 micromol/L) inhibited the H(2)O(2)-induced activation of WT hKv1.5 channels. In contrast, quercetin had no significant effect. 4. We conclude that: (i) quercetin preferentially binds to and increases the current amplitude of WT hKv1.5 channels; (ii) Ile502, an aliphatic and neutral amino acid residue residing in the S6 segment, is important in quercetin binding; and (iii) quercetin-induced changes in the properties of WT hKv1.5 channels may be foreign to its own anti-oxidant action.

[Effects of telmisartan on voltage-gated Kv1.3 and Kv1.5 potassium channels expressed in Xenopus oocytes].

OBJECTIVE: To observe the effects of telmisartan on Kv1.3 and Kv1.5 potassium channels expressed in Xenopus oocytes. METHODS: Kv1.3 and Kv1.5 potassium channel currents expressed in Xenopus oocytes were recorded and observed in the absence and presence of telmisartan using standard two-microelectrode voltage clamp techniques. RESULTS: Telmisartan resulted in a concentration- and voltage-dependent inhibition effect on Kv1.3 channel current (IC(50) 2.05 micromol/L)and on Kv1.5 channel current (IC(50) 2.37 micromol/L). CONCLUSIONS: Telmisartan blocks open-state Kv1.3 channel which could be one of the mechanisms related to its immunomodulatory and anti-atherosclerosis effect. Telmisartan also blocks open-state Kv1.5 channel which might partly account for its effect on reducing the incidence of atrial fibrillation.