Energetic evaluation of phenol wastewater treatment by reverse electrodialysis reactor using different anodes.

Efficient electrode materials are essential to convert salinity gradient energy into oxidative degradation energy and electrical energy by reverse electrodialysis reactor (REDR). In this context, comparative experiments of REDR using different anodes (Ti/IrO2-RuO2, Ti/PbO2 and Ti/Ti4O7) were conducted. The effects of output current and electrode rinse solution (ERS) flowrate on mineralization efficiency and energy output were discussed. Results demonstrated that the COD removal rate(ηCOD) rose almost linearly with output current and ERS flowrate when using Ti/Ti4O7 anode, but excessive operating conditions caused a slow increase or even decrease of ηCOD when using Ti/IrO2-RuO2 or Ti/PbO2 anodes. The order of electrode system potential loss (Eele) for the three anodes was Ti/Ti4O7> Ti/PbO2> Ti/IrO2-RuO2. High Eele was beneficial to ηCOD but had a negative effect on the net output power (Pnet) of REDR. Regardless of the applied anodes, increasing the current and decreasing the ERS flowrate was detrimental to Pnet due to higher Eele. Based on these findings, four energy efficiency parameters were defined to evaluate energy recovery from multiple perspectives by linking energy output with mineralization capacity. They were electrode efficiency (ηele), energy efficiency (EE), general current efficiency (GCE) and energy consumption (EC), respectively. Results showed that REDR with Ti/Ti4O7 anodes and suitable operating conditions achieved the optimal energy indicators and mineralization efficiency, which provided an efficient and economical option for wastewater treatment and energy recovery.

The Mechanical Properties of Gangue Paste Material for Deep Mines: An Experimental and Model Study.

Gangue paste material is mainly composed of coal gangue with particle size, which is mixed with cement. Fly ash and additives can be added to change its performance. In this paper, the influence of each component on the mechanical properties of gangue paste material was studied by an orthogonal experiment. The conversion relationship among various indexes of mechanical properties of gangue paste material and the response surface prediction model were discussed. The results show that the mechanical properties of gangue paste materials are positively correlated with the content of cement, the content of fly ash and the mass concentration, which increase with the increase of the three factors, and show the primary and secondary relationship of the content of cement > the content of fly ash > the mass concentration. A response surface prediction model of mechanical property parameters is established, which includes the first order term of the influencing factors of gangue paste material and the first order interaction term between any two factors. In the response surface prediction model of uniaxial compressive strength, splitting tensile strength, cohesion and elastic modulus, the goodness of fit test coefficients are 0.998, 0.957, 0.970 and 0.997, respectively, which proves that the model has good goodness of fit. The research results provide basic parameters for paste filling mining practice, and also provide the basis for numerical simulation of filling body value.

Electrochemical removal of synthetic methyl orange dyeing wastewater by reverse electrodialysis reactor: Experiment and mineralizing model.

In this paper, the synthetic methyl orange (MO) dyeing wastewater treated by a reverse electrodialysis reactor (REDR) with 40 member pairs was investigated first. The boron-doped diamond (BDD) and carbon felt were adopted as an anode and a cathode in the REDR. The influences of operation parameters on the chemical oxygen demand (COD) removal efficiency were detected and explored. Then, a mathematical model of organic mineralizing was developed for the REDR to predict the variation of COD removal efficiency with treating time under the different operation conditions. Finally, the energy consumption of the wastewater treated by the REDR was analyzed. The results showed that raising the working fluid flowing velocity and electrode rinse solution flowrate improved the COD removal efficiency and instantaneous current efficiency (ICE), and reduced the total energy consumption (TEC) of the REDR. Raising the initial MO concentration could significantly reduce the TEC despite the COD removal efficiency being near. Since the main energy consumed by the REDR was salinity gradient energy (SGE) from waste heat conversion or the natural environment, the energy cost of REDR treating wastewater has been reduced significantly.

P-cymene prevent high-fat diet-associated colorectal cancer by improving the structure of intestinal flora.

Objective: To investigate the preventing effect of P-cymene on high fat diet-related colorectal cancer and its mechanism. Methods: Forty Wistar rats were randomly divided into G1 group (high-fat diet), G2 group (high-fat diet + DMH), G3 group (high-fat diet + P-cymene), and G4 group (high-fat diet + DMH + P-cymene).G2 and G4 groups were subcutaneously injected with dimethylhydrazine (DMH), and G3 and G4 groups were intragastrically administered with P-cymene to investigate the effects of P-cymene on tumor formation, inflammatory factors, glucose, lipid metabolism and gut microbes. Results: No tumors were formed in the high-fat diet group (G1) or the high-fat diet + P-cymone group (G3). 7 rats (70%) of the high-fat diet + DMH group (G2) developed 8 cancerous nodules, including 6 adenocarcinomas and 2 signet ring cell carcinomas; 4 rats (40%) in the high-fat diet + DMH + P-cymene group (G4) group formed 4 cancerous nodules, all of which were adenocarcinoma. There was no significant difference in the changes of glucose and lipid metabolism in each group. After the use of P-cymene, IL-1 decreased, IL-6 increased, and LEP decreased in the G4 group.The difference was statistically significant.The contents of Candida and Unclassified Bacteria in the G3 group rats were significantly lower than those in the G1 group.At the species level comparison, compared with the G2 group, the content of Clostridium XlVa in the intestinal tract of the G2 group rats was significantly increased compared to the G1 group. Conclusion: In this study, it was found that p-cymenen can prevent the occurrence of colorectal cancer related to high-fat and high-calorie diet. The mechanism may be is reducing the expression of inflammatory factors such as IL-1 and LEP, increasing the expression of inflammatory factors of IL-6, and promoting the growth of probiotics such as bifidobacteria, isobacteria and clostridium IV in the intestinal tract.

The Anti-oxidant Monoterpene p-Cymene Reduced the Occurrence of Colorectal Cancer in a Hyperlipidemia Rat Model by Reducing Oxidative Stress and Expression of Inflammatory Cytokines.

BACKGROUND/AIM: Overexpression of inflammatory cytokines and oxidative stress increase the risk of colorectal cancer (CRC) in obesity and hyperlipidemia. The aim of this study was to investigate whether the monoterpene antioxidant p-cymene would reduce the incidence of CRC in a rat model of hyperlipidemia. MATERIALS AND METHODS: The hyperlipidemic CRC rat model was established by a high-fat diet and dimethyl hydrazine (DMH) induction. All rats received 30 mg/kg DMH to induce CRC, and were then assigned to groups with a normal diet or high-fat diet with/without 30 mg/kg/day p-cymene orally during the entire experimental period. Tumor incidence in each group, and the level of serum inflammatory cytokines and oxidative stress-related markers in intestinal tissues were measured. RESULTS: p-Cymene significantly inhibited CRC occurrence in hyperlipemic rats (p=0.024) by reducing the expression of serum inflammatory cytokines (interleukin-1 by 54.5%; interleukin-6 by 28.3%; adiponectin by 26.3%; cyclo-oxygenase-2 by 48.4%) and intestinal oxidative-stress cytokines (total antioxidant capacity by 30.4%; superoxide dismutase by 30.3%; malondialdehyde by 47.1%). CONCLUSION: p-Cymene has clinical potential to reduce the incidence of CRC in hyperlipemia.

Room-Temperature Magnetism of Ceria Nanocubes by Inductively Transferring Electrons to Ce Atoms from Nearby Oxygen Vacancy.

Ceria (CeO2) nanocubes were synthesized by a hydrothermal method and weak ferromagnetism was observed in room temperature. After ultraviolet irradiation, the saturation magnetization was significantly enhanced from ~3.18 × 10-3 to ~1.89 × 10-2 emu g-1. This is due to the increase of oxygen vacancies in CeO2 structure which was confirmed by X-ray photoelectron spectra. The first-principle calculation with Vienna ab-initio simulation package was used to illustrate the enhanced ferromagnetism mechanism after calculating the density of states (DOSs) and partial density of states (PDOSs) of CeO2 without and with different oxygen vacancies. It was found that the increase of oxygen vacancies will enlarge the PDOSs of Ce 4f orbital and DOSs. Two electrons in one oxygen vacancy are respectively excited to 4f orbital of two Ce atoms neighboring the vacancy, making these electron spin directions on 4f orbitals of these two Ce atoms parallel. This superexchange interaction leads to the formation of ferromagnetism in CeO2 at room temperature. Our work indicates that ultraviolet irradiation is an effective method to enhance the magnetism of CeO2 nanocube, and the first-principle calculation can understand well the enhanced magnetism.

Measurement system that improves the accuracy of polyp size determined at colonoscopy.

AIM: To assess the accuracy of polyp size using an endoscopic lesion measurement system (ELMS). METHODS: The accuracy of polyp size assessment was compared among measurements acquired by visual estimation, disposable graduated biopsy forceps (DGBF; used as a "scale-plate") and the ELMS. RESULTS: There were 192 polyps from 166 cases included in this study. The mean diameter of the post polypectomy measurement was 0.85±0.53 cm (range: 0.2-3.0 cm). The mean diameter by visual estimation was 1.10±0.53 cm, which was significantly different compared to the actual size of the polyp (P<0.001). The mean diameters obtained using DGBF (0.87±0.54 cm) and ELMS (0.85±0.53 cm) did not significantly differ from the actual size of the polyp. The difference between the measurements from the ELMS and DGBF was not significant. CONCLUSION: Unlike visual estimations at colonoscopy, endoscopic graduated biopsy forceps and the endoscopic lesion measurement system are accurate methods to estimate polyp size.

Notepad-like triboelectric generator for efficiently harvesting low-velocity motion energy by interconversion between kinetic energy and elastic potential energy.

Great attention has been paid to nanogenerators that harvest energy from ambient environments lately. In order to give considerable output current, most nanogenerators require high-velocity motion that in most cases can hardly be provided in our daily life. Here we report a notepad-like triboelectric generator (NTEG), which uses simple notepad-like structure to generate elastic deformation so as to turn a low-velocity kinetic energy into high-velocity kinetic energy through the conversion of elastic potential energy. Therefore, the NTEG can achieve high current output under low-velocity motion, which completely distinguishes it from tribogenerators previously reported. The factors that may affect the output performance are explored, including the number of slices, active length of slice, press speed, and vertical displacement. In addition, the working mechanism is systematically studied, indicating that the efficiency of the generator can be greatly enhanced by interconversion between kinetic energy and elastic potential energy. The short-circuit current, the open-circuit voltage, and power density are 205 µA and 470 V and 9.86 W/m(2), respectively, which is powerful enough to light up hundreds of light-emitting diodes (LEDs) and charge a commercial capacitor. Besides, NTEGs have been successfully applied to a self-powered door monitor.

Use of disposable graduated biopsy forceps improves accuracy of polyp size measurements during endoscopy.

AIM: To determine the accuracy of endoscopic polyp size measurements using disposable graduated biopsy forceps (DGBF). METHODS: Gradations accurate to 1 mm were assessed with the wire of disposable graduated biopsy forceps. When a polyp was noted, endoscopists determined the width of the polyp; then, the graduated biopsy forceps was inserted and the largest diameter of the tumor was measured. After excision, during surgery or endoscopy, the polyp was measured using the vernier caliper. RESULTS: One hundred and thirty-three colorectal polyps from 119 patients were studied. The mean diameter, by post-polypectomy measurement, was 0.92 ± 0.69 cm; 83 were < 1 cm, 36 were between 1 and 2 cm, and 14 were > 2 cm. The mean diameter, by visual estimation, was 1.15 ± 0.88 cm; compared to the actual size measured using vernier calipers, the difference was statistically significant. The mean diameter measured using the DGBF was 0.93 ± 0.68 cm; compared to the actual size measured using vernier calipers, this difference was not statistically significant. The ratio between the mean size estimated by visual estimation and the actual size was significantly different from that between the mean size estimated using the DGBF and the actual size (1.26 ± 0.30 vs 1.02 ± 0.11). CONCLUSION: The accuracy of polyp size estimation was low by visual assessment; however, it improved when the DGBF was used.

Airflow-induced triboelectric nanogenerator as a self-powered sensor for detecting humidity and airflow rate.

Humidity sensors are commonly based on the resistance change of metal oxide semiconductors, which show high sensitivity in low humidity but low sensitivity in high humidity. In this work, we design a novel humidity sensor based on the airflow-induced triboelectric nanogenerator (ATNG) that can serve as a self-powered sensor to detect humidity (especially in high humidity) and airflow rate. The output current or voltage change is investigated under different humidity (20-100% relative humidity) at fixed airflow rate and different airflow rates (15-25 L/min) at a fixed humidity. The working principle of the ATNG-based sensor is illustrated. We find that both output current and voltage can serve as a variable for detecting humidity, while only the output current can serve as a variable for determining airflow rate. Our study demonstrates an innovative approach toward detection of humidity and airflow rate with advantages of self-power, multifunction, low cost, simple fabrication, and high sensitivity.

Photocatalytic activity of ZnWO4: band structure, morphology and surface modification.

Photocatalytic degradation of organic contaminants is an important application area in solar energy utilization. To improve material photocatalytic properties, understanding their photocatalytic mechanism is indispensable. Here, the photocatalytic performance of ZnWO4 nanocrystals was systematicly investigated by the photodegradation of tetraethylated rhodamine (RhB) under simulated sunlight irradiation, including the influence of morphology, AgO/ZnWO4 heterojunction and comparison with CoWO4 nanowires. The results show that the photocatalytic activity of ZnWO4 is higher than that of CoWO4, and the ZnWO4 nanorods exhibit better photocatalytic activity than that of ZnWO4 nanowires. In addition, the mechanism for the difference of the photocatalytic activity was also investigated by comparison of their photoluminescence and photocurrents. AgO nanoparticles were assembled uniformly on the surface of ZnWO4 nanowires to form a heterojunction that exhibited enhanced photocatalytic activity under irradiation at the initial stage. We found that a good photocatalyst should not only have an active structure for electrons directly to transfer from the valence band to the conduction band without the help of phonons but also a special electronic configuration for the high mobility, to ensure more excited electrons and holes in a catalytic reaction.

Smooth muscle enfoldment internal sphincter construction after intersphincteric resection for rectal cancer.

OBJECTIVE: To assess smooth muscle enfoldment and internal sphincter construction (SMESC) for improvement of continence after intersphincteric resection (ISR) for rectal cancer. METHODS: Twenty-four Bama miniature pigs were randomly divided into a conventional ISR group and experimental SMESC group, with 12 pigs in each group. The proximal sigmoid colon was anastomosed directly to the anus in the ISR group. In the SMESC group, internal sphincter construction was performed. At 12 weeks before and after surgery, rectal resting pressure and anal canal length were assessed. Three-dimensional ultrasound was used to determine the thickness of the internal sphincter. After the animals were sacrificed, the rectum and anus were resected and pathological examinations were performed to evaluate the differences in sphincter thickness and muscle fibers. RESULTS: All 24 animals in the SMESC group and the ISR group survived the surgery. Twelve weeks post-surgery, the rectal resting pressure, length of the anal high-pressure zone and the postoperative internal sphincter thickness for the ISR group were significantly lower than for the SMESC group. There was a thickened area (about 2 cm) above the anastomotic stoma among animals from the SMESC group; in addition, the smooth muscles were significantly enlarged and enfolded when compared to the ISR group. CONCLUSION: This animal model study shows that the SMESC procedure achieved acceptable reconstruction of the internal anal neo-sphincter (IAN/S), without increasing surgical risk. However, the findings in this experimental animal model must be confirmed by clinical trials to determine the safety and efficacy of this procedure in clinical practice.

[Study on accuracy of endoscopic polyp size measurement by disposable graduated biopsy forceps].

OBJECTIVE: To study the accuracy of endoscopic polyp size measurement by disposable graduated biopsy forceps (DGBF). METHODS: Accurate gradation of 1 mm was made in the wire of disposable graduated biopsy forceps, which was used to measure the size of tumors under endoscopy. Fifty-eight polyps from 43 patients underwent endoscopy in our department from May to June 2013 were enrolled. Size of polyp was measured and compared among DGBF, routine estimation and direct measurement after resection. The accuracy of polyp size measurement was investigated by four colonoscopists who had finished at least 2000 procedures of colonoscopy. RESULTS: The mean diameter of post-polypectomy measurement was (1.02±0.84) cm. Diameter was less than 1 cm in 36 polyps, 1 to 2 cm in 15, and over 2 cm in 7. The mean diameter of visual estimation was (1.29±1.07) cm, and the difference was significant as compared with actual size (P=0.000). The mean diameter measured by DGBF was (1.02±0.82) cm, and the difference was not significant as compared with actual size (P=0.775). The ratio of visual estimation to actual size was 1.29±0.31, and DGBF estimation to actual size was 1.02±0.11 with significant difference (P=0.000). The accurate rate of DGBF in estimating polyp size was 77.6% (45/58), which was obviously higher as compared to visual estimation [19.0% (11/58), P=0.000]. CONCLUSION: The accuracy of DGBF as a scale in the estimation of poly size increases as compared to visual estimation.

Dietary flavonoid for preventing colorectal neoplasms.

BACKGROUND: Flavonoids are polyphenolic compounds that are distributed widely in the plant kingdom; they are especially abundant in fruits and vegetables. More than 5,000 individual flavonoids have been identified and classified into more than 10 subgroups according to their chemical structure. Flavonoids have many possible biological effects that may play a role in cancer prevention. Prior studies have suggested that a high intake of flavonoids may help prevent cancer. OBJECTIVES: To assess the effect of dietary flavonoids on the incidence of colorectal adenoma and CRC. SEARCH METHODS: Eligible studies were searched up until July 2011 in the Cochrane Library, PubMed, EMBASE and other CINAHL databases and reference lists of previous reviews. SELECTION CRITERIA: All prospective, controlled interventional studies and observational studies that either assessed the association between flavonoids and risk of CRC incidence or colorectal adenoma recurrence were included. DATA COLLECTION AND ANALYSIS: At least two investigators independently reviewed the material and extracted the data according to the inclusion criteria; in addition, the methodological quality of the studies was assessed. MAIN RESULTS: Eight studies with 390,769 participants were included. Five studies used a prospective cohort design, two were case-control studies and one a randomised controlled trial (RCT). The methodological quality was measured using the Newcastle-Ottawa scale (NOS). The three prospective cohort studies were of high methodological quality, and two were of medium quality. The two case-control studies were of medium methodological quality.The results form the studies assessing associations between flavonoids, colorectal cancer and adenomas were contradictory. There was no evidence that total flavonoid intake reduced the risk of colorectal neoplasms. The evidence for Isoflavones, Flavonols, Flavones and Flavanones was conflicting. For Flavan-3-ols, the results from two studies suggested that increased intake of Flavan-3-ols reduced the risk of both CRC and colorectal adenomas. A statistically significant reduced risk of CRC was found with high intake of epicatechin. There was medium quality evidence to support that increased intake of procyanidin and phytoestrogen could reduced the incidence of CRC. There was no evidence that suggested that high anthocyanin intake had an inverse association with colorectal adenomas. AUTHORS' CONCLUSIONS: There is insufficient and conflicting evidence regarding flavonoid intake and the prevention of colorectal neoplasms. It is difficult to determine flavonoid intake. Therefore, more evidence is needed to clarify the association between flavonoids and colorectal neoplasms.

Anal fistula plug vs mucosa advancement flap in complex fistula-in-ano: A meta-analysis.

AIM: To investigate the efficacy of the anal fistula plug (AFP) compared to the mucosa advancement flap (MAF), considered the best procedure for patients with a complex anal fistula. METHODS: The literature search included PubMed, EMBASE, Cochrane Library and OVID original studies on the topic of AFP compared to MAF for complex fistula-in-ano that had a deadline for publication by April 2011. Randomized controlled trials, controlled clinical trials and prospective cohort studies were included in the review. After information collection, a meta-analysis was performed using data on overall success rates as well as incidence of incontinence and morbidity. The quality of postoperative life was also included with the clinical results. RESULTS: Six studies involving 408 patients (AFP = 167, MAF = 241) were included in the meta-analysis. The differences in the overall success rates and incidence of fistula recurrence were not statistically significant between the AFP and MAF [risk difference (RD) = -0.12, 95%CI: -0.39 - 0.14; RD = 0.13; 95%CI: -0.18 - 0.43, respectively]. However, for the AFP, the risk of postoperative impaired continence was lower (RD = -0.08, 95%CI: -0.15 - -0.02) as was the incidence of other complications (RD = -0.06, 95%CI: -0.11 - -0.00). The postoperative quality of life, for patients treated using the AFP was superior to that of the MAF patients. Patients treated with the AFP had less persistent pain of a shorter duration and the healing time of the fistula and hospital stay were also reduced. CONCLUSION: The AFP is an effective procedure for patients with a complex anal fistula; it has the same success rate but a lower risk of complications than the MAF and may also be associated with an improved postoperative quality of life. Additional evidence is needed to confirm these findings.

[Distribution characteristics of colorectal neoplasm in 4450 patients and implication for colorectal cancer screening].

OBJECTIVE: To study the distribution characteristics of colorectal neoplasm and evaluate the implication for colorectal cancer screening. METHODS: A total of 17,939 colonoscopies were performed in the National Center of Colorectal Surgery between October 2004 and June 2009. Characteristics of colorectal neoplasm including anatomical distribution, sex, and age were investigated. RESULTS: Colorectal neoplasm was found in 24.8% (4450/17,939) of the patients during colonoscopy, including adenomatous polyp (n=3410, 19.0%) and adenocarcinoma (n=1040, 5.8%). The prevalence of colorectal neoplasm was higher in male and significantly increased in patients older than 40 years. 63.3% of the lesions located at the distal colon (sigmoid colon and rectum) and 36.7% at the proximal colon (36.7%). In patients with adenomatous polyp, 52.8% (1802/3410) of the lesions were at the distal colon, 30.8% (1049/3410) at the proximal colon, and 16.4% (559/3410) at both distal and proximal colon. In patients with carcinoma (n=1040), 921 (88.6%) lesions located at the distal colon, 118 (11.3%) at the proximal colon, and 1 (0.1%) at both segments. CONCLUSION: Sigmoidoscopy is inadequate for colorectal cancer screening as compared to colonoscopy.

Src family protein tyrosine kinase (PTK) modulates the effect of SGK1 and WNK4 on ROMK channels.

WNK4 (with no lysine kinase 4) inhibits ROMK channel activity in the distal nephron by stimulating clathrin-dependent endocytosis, an effect attenuated by SGK1 (serum-glucocorticoids-induced kinase)-mediated phosphorylation. It has been suggested that increased ROMK activity because of SGK1-mediated inhibition of WNK4 plays a role in promoting renal K secretion in response to elevated serum K or high K (HK) intake. In contrast, intravascular volume depletion also increases SGK1 activity but fails to stimulate ROMK channels and K secretion. Because HK intake decreases Src family protein tyrosine kinase (PTK) activity an inhibitor of ROMK channels, it is possible that Src family PTK may modulate the effects of SGK1 on WNK4. Here, we show that c-Src prevents SGK1 from attenuating WNK4's inhibition of ROMK activity. This effect of c-Src was WNK4-dependent because c-Src had no effect on ROMK harboring mutation at the site of c-Src phosphorylation (R1Y337A) in the absence of WNK4. Moreover, expression c-Src diminished the SGK1-mediated increase in serine phosphorylation of WNK4, suggesting that c-Src enhances WNK4-mediated inhibition of ROMK channels by suppressing the SGK1-induced phosphorylation. This notion is also supported by the observation that c-Src was not able to modulate the interaction between SGK1 and WNK4 mutants (WNK4(S1169A) or WNK4(S1169D)) in which an SGK1-phosphorylation site (serine 1169) was mutated by alanine or aspartate. We conclude that c-Src inhibits SGK1-mediated phosphorylation hereby restoring the WNK4-mediated inhibition of ROMK channels thus suppressing K secretion.

Angiotensin II signaling increases activity of the renal Na-Cl cotransporter through a WNK4-SPAK-dependent pathway.

Mutations in the kinase WNK4 cause pseudohypoaldosteronism type II (PHAII), a syndrome featuring hypertension and high serum K(+) levels (hyperkalemia). WNK4 has distinct functional states that regulate the balance between renal salt reabsorption and K(+) secretion by modulating the activities of renal transporters and channels, including the Na-Cl cotransporter NCC and the K(+) channel ROMK. WNK4's functions could enable differential responses to intravascular volume depletion (hypovolemia) and hyperkalemia. Because hypovolemia is uniquely associated with high angiotensin II (AngII) levels, AngII signaling might modulate WNK4 activity. We show that AngII signaling in Xenopus oocytes increases NCC activity by abrogating WNK4's inhibition of NCC but does not alter WNK4's inhibition of ROMK. This effect requires AngII, its receptor AT1R, and WNK4, and is prevented by the AT1R inhibitor losartan. NCC activity is also increased by WNK4 harboring mutations found in PHAII, and this activity cannot be further augmented by AngII signaling, consistent with PHAII mutations providing constitutive activation of the signaling pathway between AT1R and NCC. AngII's effect on NCC is also dependent on the kinase SPAK because dominant-negative SPAK or elimination of the SPAK binding motif in NCC prevent activation of NCC by AngII signaling. These effects extend to mammalian cells. AngII increases phosphorylation of specific sites on SPAK and NCC that are necessary for activation of each in mpkDCT cells. These findings place WNK4 in the signaling pathway between AngII and NCC, and provide a mechanism by which hypovolemia maximizes renal salt reabsoprtion without concomitantly increasing K(+) secretion.

Echinacea in infection.

Ongoing studies have developed strategies for identifying key bioactive compounds and chemical profiles in Echinacea with the goal of improving its human health benefits. Antiviral and antiinflammatory-antipain assays have targeted various classes of chemicals responsible for these activities. Analysis of polar fractions of E. purpurea extracts showed the presence of antiviral activity, with evidence suggesting that polyphenolic compounds other than the known HIV inhibitor, cichoric acid, may be involved. Antiinflammatory activity differed by species, with E. sanguinea having the greatest activity and E. angustifolia, E. pallida, and E. simulata having somewhat less. Fractionation and studies with pure compounds indicate that this activity is explained, at least in part, by the alkamide constituents. Ethanol extracts from Echinacea roots had potent activity as novel agonists of TRPV1, a mammalian pain receptor reported as an integrator of inflammatory pain and hyperalgesia and a prime therapeutic target for analgesic and antiinflammatory drugs. One fraction from E. purpurea ethanol extract was bioactive in this system. Interestingly, the antiinflammatory compounds identified to inhibit prostaglandin E(2) production differed from those involved in TRPV1 receptor activation.

An SGK1 site in WNK4 regulates Na+ channel and K+ channel activity and has implications for aldosterone signaling and K+ homeostasis.

The steroid hormone aldosterone is secreted both in the setting of intravascular volume depletion and hyperkalemia, raising the question of how the kidney maximizes NaCl reabsorption in the former state while maximizing K(+) secretion in the latter. Mutations in WNK4 cause pseudohypoaldosteronism type II (PHAII), a disease featuring increased renal NaCl reabsorption and impaired K(+) secretion. PHAII-mutant WNK4 achieves these effects by increasing activity of the Na-Cl cotransporter (NCC) and the Na(+) channel ENaC while concurrently inhibiting the renal outer medullary K(+) channel (ROMK). We now describe a functional state for WNK4 that promotes increased, rather than decreased, K(+) secretion. We show that WNK4 is phosphorylated by SGK1, a mediator of aldosterone signaling. Whereas wild-type WNK4 inhibits the activity of both ENaC and ROMK, a WNK4 mutation that mimics phosphorylation at the SGK1 site (WNK4(S1169D)) alleviates inhibition of both channels. The net result of these effects in the kidney would be increased K(+) secretion, because of both increased electrogenic Na(+) reabsorption and increased apical membrane K(+) permeability. Thus, modification at the PHAII and SGK1 sites in WNK4 impart opposite effects on K(+) secretion, decreasing or increasing ROMK activity and net K(+) secretion, respectively. This functional state for WNK4 would thus promote the desired physiologic response to hyperkalemia, and the fact that it is induced downstream of aldosterone signaling implicates WNK4 in the physiologic response to aldosterone with hyperkalemia. Together, the different states of WNK4 allow the kidney to provide distinct and appropriate integrated responses to intravascular volume depletion and hyperkalemia.