Effects of Chalcogen Atoms on Excited-State Double-Proton Transfer Behavior for 3,6-bis(4,5-Dihydroxyoxazo-2-yl)benzene-1,2-diol Derivatives: A Computational Investigation.

The impact of the chalcogen atomic electronegativity (O, S, and Se atoms) of new organic molecules on excited-state dynamical reactions is self-evident. Inspired by this kind of distinguished photochemical characteristic, in this work, we performed a computational investigation of chalcogen-substituted 3,6-bis(4,5-dihydroxyoxazo-2-yl)benzene-1,2-diol (BDYBD) derivatives (i.e., BDYBD-O, BDYBD-S, and BDYBD-Se). In this paper, we pay close attention to characteristic BDYBD derivatives that contain intramolecular double hydrogen bonds (O1-H2···N3 and O4-H5···N6). The main goal of this study was to explore how changes in atomic electronegativity affect the way hydrogen bonds interact and how excited molecules affect transfer protons. We go into further detail in the main text of the paper. By fixing our attention to geometrical variations and infrared (IR) vibrational spectra between the S0 and S1 states, exploring hydrogen bonding behaviors using the core-valence bifurcation (CVB) index, and simulating hydrogen bonding energy (EHB) via the atom in molecule (AIM) method, we clarified the photo-induced strengthened dual hydrogen bonding interactions that facilitate the excited-state dual-proton transfer (ESDPT) behavior of BDYBD derivatives. The reorganization of charge stemming from photoexcitation further verifies the tendencies of ESDPT reactions. We relied on constructing potential energy surfaces (PESs) by adopting a restrictive optimization approach, and herein, we finally clarify the gradual ESDPT mechanism of BDYBD derivatives. Particularly, we confirm that the variation in chalcogen atomic electronegativity has a regulatory effect on the ESDPT behavior of BDYBD derivatives; that is, the lower the atomic electronegativity, the more favorable it is for the gradual ESDPT reaction.

Occurrence and influencing factors of antibiotics and antibiotic resistance genes in sediments of the largest multi-habitat lakes in Northern China.

Baiyangdian Lake is a typical and largest multi-habitat lake in the North plain of China. To understand the generation and transmission of antibiotics resistance genes (ARGs) in multi-habitat lakes, the contents of nutrients (TC, TOC, TN, TP and TS), heavy metals (Zn, Cr, Ni, Cu, Pb, As, Cd and Hg), 22 antibiotics, 16S-rRNA(16S), Class I integron (intI1) and 20 ARGs were determined. Samples were taken from the Fuhe river, river estuaries, reed marshes, living area, fish ponds and open water of Baiyangdian Lake. The results showed that quinolones were the main pollutants in six habitats, and the content range was ND-104.94 ng/g. Thereinto, aac (6') -IB, blaTEM-1, ermF, qnrA, qnrD, tetG, sul1, sul2 and tetM were detected in all the analyzed samples. The absolute abundance of sul1 was the highest (5.25 × 105 copies/g-6.21 × 107 copies/g) in most of the samples. In these different habitats, the abundance of antibiotics and ARGs in river estuary was the highest, and that in reed marshes was the lowest. There was a significant positive correlation between the abundance of heavy metals (Cu, Pb, Zn, Ni, Cd, Hg) and the absolute abundance of 11 ARGs (P < 0.01). Redundancy analysis showed that Cu, Zn, intI1, TP and macrolides were the important factors affecting the distribution of ARGs. Our finding provides a more likely driving and influencing factor for the transmission of ARGs in lakes with complex and diverse habitats.

Evaluation of the Potential Protective Effects of Lactobacillus Strains against Helicobacter pylori Infection: A Randomized, Double-Blinded, Placebo-Controlled Trial.

Background: The beneficial effects of probiotic supplementation standard antibiotic therapies for Helicobacter pylori infection have been verified, but the ability of probiotic monotherapy to eradicate H. pylori remains unclear. Aim: To evaluate the accuracy and efficacy of specific Lactobacillus strains against H. pylori infection. Methods: Seventy-eight patients with H. pylori infection were treated with strain L. crispatus G14-5M (L. crispatus CCFM1118) or L. helveticus M2-09-R02-S146 (L. helveticus CCFM1121) or L. plantarum CCFM8610 at a dose of 2 g twice daily for one month. 14C-urea breath test, the gastrointestinal symptom rating scale, serum pepsinogen concentrations, and serum cytokine concentrations of patients were measured at baseline and end-of-trial to analyze the effect of the Lactobacillus strains in eradicating H. pylori infection and reducing gastrointestinal discomfort in patients. In addition, the composition and abundance of the intestinal microbiota of patients were also measured at end-of-trial. Results: The 14C-urea breath test value of the three Lactobacillus treatment groups had decreased significantly, and the eradication rate of H. pylori had increased by the end of the trial. In particular, the eradication rate in the G14-5M treatment group was significantly higher than the placebo group (70.59% vs. 15.38%, P=0.0039), indicating that one-month administration of the G14-5M regimen was sufficient to eradicate H. pylori infection. The ingestion of Lactobacillus strains also ameliorated the gastrointestinal symptom rating scale scores, and the serum interleukin-8 concentrations of H. pylori-infected patients appeared to modulate the gut microbiota of patients. However, none of the Lactobacillus strains had a significant effect on general blood physiological characteristics, serum tumor necrosis factor α concentrations, or serum pepsinogen concentrations in the patients. Conclusion: Three Lactobacillus strains significantly alleviate the gastrointestinal discomfort and the gastric inflammatory response of H. pylori-infected patients. The activity of probiotics in eradicating H. pyloriinfection may be species/strain specific.

Meta-analysis of the efficacy of probiotic-supplemented therapy on the eradication of H. pylori and incidence of therapy-associated side effects.

Traditional therapies for Helicobacter pylori (H. pylori) infection remain hindered by the antibiotic resistance of the pathogen and the poor therapeutic compliance of patients. To address these issues, probiotics have been added as an adjunctive therapy. This meta-analysis aimed to evaluate the efficacy of probiotic supplementation during standard therapy on the eradication rate of H. pylori infection and incidence of therapy-related side effects. Four online databases were searched for eligible studies without language restriction. Review Manager (REVMAN, Version 5.3) was used to perform all data analyses. Forty articles including 5792 patients met our criteria and were included in the analysis. Notably, probiotic supplementation improved the eradication rate by approximately 10% relative to the control group [odds ratio (OR), 1.94, 95% confidence interval (CI): 1.70-2.22, P < 0.00001]. The incidence of total side effects (OR, 0.56, 95% CI: 0.45-0.70, P < 0.00001) and individual symptoms (e.g., diarrhea, vomiting and nausea, constipation, epigastric pain, taste disturbance) also decreased significantly with probiotic supplementation. No other differences in side effects were observed between the experimental and control groups. Moreover, a longer duration (≥10 days) of probiotic treatment had positive effects on both eradication rate of H. pylori and incidence of overall side effects.

Enhanced Phosphorus Locking by Novel Lanthanum/Aluminum-Hydroxide Composite: Implications for Eutrophication Control.

Lanthanum (La) bearing materials have been widely used to remove phosphorus (P) in water treatment. However, it remains a challenge to enhance phosphate (PO4) adsorption capacity and La usage efficiency. In this study, La was coprecipitated with aluminum (Al) to obtain a La/Al-hydroxide composite (LAH) for P adsorption. The maximum PO4 adsorption capacities of LAH (5.3% La) were 76.3 and 45.3 mg P g-1 at pH 4.0 and 8.5, which were 8.5 and 5.3 times higher than those of commercially available La-modified bentonite (Phoslock, 5.6% La), respectively. P K-edge X-ray absorption near edge structure analysis showed that PO4 was preferentially bonded with Al under weakly acid conditions (pH 4.0), while tended to associate with La under alkaline conditions (pH 8.5). La LIII-edge extended X-ray absorption fine structure analysis indicated that PO4 was bonded on La sites by forming inner sphere bidentate-binuclear complexes and oxygen defects exhibited on LAH surfaces, which could be active adsorption sites for PO4. The electrostatic interaction, ligand exchange, and oxygen defects on LAH surfaces jointly facilitated PO4 adsorption but with varied contribution under different pH conditions. The combined contribution of two-component of La and Al may be an important direction for the next generation of commercial products for eutrophication mitigation.

Nanobubbles at Hydrophilic Particle-Water Interfaces.

The puzzling persistence of nanobubbles breaks Laplace's law for bubbles, which is of great interest for promising applications in surface processing, H2 and CO2 storage, water treatment, and drug delivery. So far, nanobubbles have mostly been reported on hydrophobic planar substrates with atomic flatness. It remains a challenge to quantify nanobubbles on rough and irregular surfaces because of the lack of a characterization technique that can detect both the nanobubble morphology and chemical composition inside individual nanobubble-like objects. Here, by using synchrotron-based scanning transmission soft X-ray microscopy (STXM) with nanometer resolution, we discern nanoscopic gas bubbles of >25 nm with direct in situ proof of O2 inside the nanobubbles at a hydrophilic particle-water interface under ambient conditions. We find a stable cloud of O2 nanobubbles at the diatomite particle-water interface hours after oxygen aeration and temperature variation. The in situ technique may be useful for many surface nanobubble-related studies such as material preparation and property manipulation, phase equilibrium, nucleation kinetics, and relationships with chemical composition within the confined nanoscale space. The oxygen nanobubble clouds may be important in modifying particle-water interfaces and offering breakthrough technologies for oxygen delivery in sediment and/or deep water environments.

Pyrolysis Treatment of Chromite Ore Processing Residue by Biomass: Cellulose Pyrolysis and Cr(VI) Reduction Behavior.

The pyrolysis treatment with biomass is a promising technology for the remediation of chromite-ore-processing residue (COPR). However, the mechanism of this process is still unclear. In this study, the behavior of pyrolysis reduction of Cr(VI) by cellulose, the main component of biomass, was elucidated. The results showed that the volatile fraction (VF) of cellulose, ie. gas and tar, was responsible for Cr(VI) reduction. All organic compounds, as well as CO and H2 in VF, potentially reduced Cr(VI). X-ray absorption near-edge structure (XANES) spectroscopy and extended X-ray absorption fine-structure (EXAFS) spectroscopy confirmed the reduction of Cr(VI) to Cr(III) and the formation of amorphous Cr2O3. The remnant Cr(VI) content in COPR can be reduced below the detection limit (2 mg/kg) by the reduction of COPR particle and extension of reaction time between VF and COPR. This study provided a deep insight on the co-pyrolysis of cellulose with Cr(VI) in COPR and an ideal approach by which to characterize and optimize the pyrolysis treatment for COPR by other organics.

Binding behavior of receptor binding domain of the SARS-CoV-2 virus and ivermectin.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), sparked an international debate on effective ways to prevent and treat the virus. Specifically, there were many varying opinions on the use of ivermectin (IVM) throughout the world, with minimal research to support either side. IVM is an FDA-approved antiparasitic drug that was discovered in the 1970s and was found to show antiviral activity. The objective of this study is to examine the binding behavior and rates of association and dissociation between SARS-CoV-2 receptor binding domain (RBD), IVM, and their combination using aminopropylsilane (APS) biosensors as surrogates for the hydrophobic interaction between the viral protein and human angiotensin-converting enzyme 2 (ACE2) receptors to determine the potential of IVM as a repurposed drug for SARS-CoV-2 prevention and treatment. The IVM, RBD, and combination binding kinetics were analyzed using biolayer interferometry (BLI) and validated with multiple in silico techniques including protein-ligand docking, molecular dynamics simulation, molecular mechanics-generalized Born surface area (MM-GBSA), and principal component analysis (PCA). Our results suggest that with increasing IVM concentrations the association rate with the hydrophobic biosensor increases with a simultaneous decrease in dissociation. Significant kinetic changes to RBD, when combined with IVM, were found only at a concentration a thousand times the approved dosage with minimal changes found over a 35-min time period. Our study suggests that IVM is not an effective preventative or treatment method at the currently approved dosage.

Impact of suspended inorganic particles on phosphorus cycling in the Yellow River (China).

Phosphorus (P) in water and sediment in the Yellow River was measured for 21 stations from the source to the Bohai Sea in 2006-2007. The average total particulate matter (TPM) increased from 40 mg/L (upper reaches) to 520 mg/L (middle reaches) and 950 mg/L in the lower reaches of the river. The average dissolved PO4 concentration (0.43 µmol/L) was significantly higher than that in 1980's but lower than the world average level despite high nutrient input to the system. Much of the P input was removed by adsorption, which was due to the high TPM rather than the surface activity of the particles since they had low labile Fe and low affinity for P. The sediment was a sink for P in the middle to lower reaches but not in the upper to middle reaches. TPM has been reduced by more than an order of magnitude due to artificial dams operating over recent decades. Modeling revealed that TPM of 0.2-1 g/L was a critical threshold for the Yellow River, below which most of the phosphate input cannot be removed by the particles and may cause eutrophication. These findings are important for river management and land-ocean modeling of global biogeochemical P cycling.

Temporal Variation of SARS-CoV-2 Levels in Wastewater from a Meat Processing Plant.

Wastewater-based surveillance (WBS) on SARS-CoV-2 has been proved to be an effective approach to estimate the prevalence of COVID-19 in communities and cities. However, its application was overlooked at smaller scale, such as a single facility. Meat processing plants are hotspots for COVID-19 outbreaks due to their unique environment that are favorable for the survival and persistence of SARS-CoV-2. This is the first known WBS study in meat processing plants. The goal was to understand the temporal variation of the SARS-CoV-2 levels in wastewater from a meat processing plant in Canada during a three-month campaign and to find any correlation with clinically confirmed cases in the surrounding city area. Higher SARS-CoV-2 concentrations and detection frequencies were observed in the solid fraction compared to the liquid fraction of the wastewater. The viruses can be preserved in the solid fraction of wastewater for up to 12 days. The wastewater virus level did not correlate to the city-wide COVID-19 cases due to the unmatching scales. WBS on SARS-CoV-2 in meat processing plants can be useful for identifying COVID-19 outbreaks in the facility and serve as an effective alternative when resources for routine individual testing are not available.

Incorporation of Selenium Derived from Nanoparticles into Plant Proteins in Vivo.

Diets comprising selenium-deficient crops have been linked to immune disorders and cardiomyopathy. Selenium nanoparticles (SeNPs) have emerged as a promising nanoplatform for selenium-biofortified agriculture. However, SeNPs fail to reach field-scale applications due to a poor understanding of the fundamental principles of its behavior. Here, we describe the transport, transformation, and bioavailability of SeNPs through a combination of in vivo and in vitro experiments. We show synthesized amorphous SeNPs, when sprayed onto the leaves of Arabidopsis thaliana, are rapidly biotransformed into selenium(IV), nonspecifically incorporated as selenomethionine (SeMet), and specifically incorporated into two selenium-binding proteins (SBPs). The SBPs identified were linked to stress and reactive oxygen species (mainly H2O2 and O2-) reduction, processes that enhance plant growth and primary root elongation. Selenium is transported both upwards and downwards in the plant when SeNPs are sprayed onto the leaves. With the application of Silwet L-77 (a common agrochemical surfactant), selenium distributed throughout the whole plant including the roots, where pristine SeNPs cannot reach. Our results demonstrate that foliar application of SeNPs promotes plant growth without causing nanomaterial accumulation, offering an efficient way to obtain selenium-fortified agriculture.

XANES analysis of spectral properties and structures of arsenate adsorption on TiO(2) surfaces.

X-ray absorption near-edge structure (XANES) of arsenate adsorption on TiO(2) surfaces was calculated using self-consistent multiple-scattering methods, allowing a structural analysis of experimental spectra. A quantitative analysis of the effect of disorder revealed that the broadening and weakening of the characteristic absorption in experimental XANES was due to the structural disorder of the arsenate-TiO(2) adsorption system. The success with calculating the scattering amplitude of a specific set of paths using the path expansion approach enables the scattering contributions of different coordination shells to the XANES to be sorted out. The results showed that the scattering resonances from high-level shells inherently overlapped onto the first-shell scattering amplitudes, and formed the fine structures in the XANES region. A variation in one oscillatory feature could be due to several structural changes affecting specific single/multiple-scattering amplitudes. Therefore, direct assignments of spectral features with structural elements should be based on adequate theoretical analysis.

Environmental Effects on Viable Virus Transport and Resuspension in Ventilation Airflow.

To understand how SARS-CoV-2 spreads indoors, in this study bovine coronavirus was aerosolized as simulant into a plexiglass chamber with coupons of metal, wood and plastic surfaces. After aerosolization, chamber and coupon surfaces were swiped to quantify the virus concentrations using quantitative polymerase chain reaction (qPCR). Bio-layer interferometry showed stronger virus association on plastic and metal surfaces, however, higher dissociation from wood in 80% relative humidity. Virus aerosols were collected with the 100 L/min wetted wall cyclone and the 50 L/min MD8 air sampler and quantitated by qPCR. To monitor the effect of the ventilation on the virus movement, PRD1 bacteriophages as virus simulants were disseminated in a ¾ scale air-conditioned hospital test room with twelve PM2.5 samplers at 15 L/min. Higher virus concentrations were detected above the patient's head and near the foot of the bed with the air inlet on the ceiling above, exhaust bottom left on the wall. Based on room layout, air measurements and bioaerosol collections computational flow models were created to visualize the movement of the virus in the room airflow. The addition of air curtain at the door minimized virus concentration while having the inlet and exhaust on the ceiling decreased overall aerosol concentration. Controlled laboratory experiments were conducted in a plexiglass chamber to gain more insight into the fundamental behavior of aerosolized SARS-CoV-2 and understand its fate and transport in the ambient environment of the hospital room.

Binding behavior of spike protein and receptor binding domain of the SARS-CoV-2 virus at different environmental conditions.

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the cause of the COVID-19 pandemic that originated in China in December 2019. Although extensive research has been performed on SARS-CoV-2, the binding behavior of spike (S) protein and receptor binding domain (RBD) of SARS-CoV-2 at different environmental conditions have yet to be studied. The objective of this study is to investigate the effect of temperature, fatty acids, ions, and protein concentration on the binding behavior and rates of association and dissociation between the S protein and RBD of SARS-CoV-2 and the hydrophobic aminopropylsilane (APS) biosensors using biolayer interferometry (BLI) validated with molecular dynamics simulation. Our results suggest three conditions-high ionic concentration, presence of hydrophobic fatty acids, and low temperature-favor the attachment of S protein and RBD to hydrophobic surfaces. Increasing the temperature within an hour from 0 to 25 °C results in S protein detachment, suggesting that freezing can cause structural changes in the S protein, affecting its binding kinetics at higher temperature. At all the conditions, RBD exhibits lower dissociation capabilities than the full-length S trimer protein, indicating that the separated RBD formed stronger attachment to hydrophobic surfaces compared to when it was included in the S protein.

The spatial variations of water quality and effects of water landscape in Baiyangdian Lake, North China.

Baiyangdian Lake (BYD), a large shallow lake in North China, has complex water landscape patterns that are underlies spatial variations in water quality. In this study, we collected 61 water samples from three water landscapes (reed littoral zones, fish ponds, and open water) and analyzed them for water quality parameters, such as dissolved organic carbon (DOC), total nitrogen (TN), and total phosphorus (TP). Water landscape distribution (determined using remote sensing imagery) was then used to assess correlations between water quality parameters and water landscape proportion in differently scaled buffer zones. There was substantial variation across all subareas, with TN and TP concentrations ranging from 0.90 to 4.10 mg/L and 0.06 to 0.18 mg/L, respectively, in class IV of water quality as a whole. Spatial variations in water quality were mainly caused by water landscape distribution and external nutrient inputs. There were negative correlations between DOC, TN, and TP concentrations and the area proportion of reed littoral zones in the 300 and 500 m buffers. In contrast, DOC, TN, and TP concentrations were significantly positively correlated with the area proportion of fish ponds in the 100 m buffer. Furthermore, compared with reed littoral zones, a lower ratio of nitrogen to phosphorus and a higher proportion of dissolved organic nitrogen and tyrosine-like proteins were found in fish ponds. These effects were mainly attributed to the development of internal sediment loadings due to nutrient exchange across the sediment-water interface. Therefore, dredging-based sediment removal from fish ponds should be considered to suppress internal phosphorus loading and accelerate recovery of the BYD ecosystem.

Effect of Multimedia Health Education on Psychological Burden, Quality of Life Ability, and Self-Efficacy of Congenital Microtia.

Aims: To investigate the effects of multimedia health education on psychological burden, quality of life, and self-efficacy of patients with congenital microtia. Materials and Methods: Eighty cases of patients with congenital microtia treated and cared for in our hospital from June 2018 to June 2022 were selected according to the numerical table method as retrospective study subjects and divided into 40 cases each in the comparison group and the observation group. The comparison group implemented conventional health education and discharge instruction, and the observation group implemented multimedia health education care to compare the effects of self-efficacy, self-care ability and psychological burden of patients in the two groups. Results: Before care, the two groups had no statistically significant difference in the quality of life scores (P > 0.05). Aftercare, the mental vitality scores, social interaction scores, emotional limitation scores, and mental status of patients in the observation group were significantly higher than those in the comparison group (P < 0.05). Before nursing care, there was no statistically significant difference in the nursing ability and anxiety-depression scores between the two groups (P > 0.05). After nursing care, the health knowledge level, self-care skills, self-care responsibility, and self-concept of the observation group were higher than the comparison group, while the depression-emotional disorder scores were significantly lower than the comparison group (P < 0.05). Conclusion: Routine health education and discharge instruction combined with multimedia health education care can effectively improve the quality of life of patients with congenital microtia, reduce adverse emotions, and improve patients' sense of self-efficacy.

[Pollution Characteristics and Risk Assessment of Nutrients and Heavy Metals in Sediments of the Fuhe River Influenced Area, Baiyangdian Lake].

Based on the flow direction of the Fuhe River into Baiyangdian Lake, the impacted area of the Fuhe River was divided into 6 subareas, and sediments from 48 sites were collected in November 2020. The characteristics and risks of sediment nutrients and heavy metal pollution in these six subareas were investigated. The results showed that the average ω(TN), ω(TP), and ω(TOC) were 1841 mg·kg-1, 769 mg·kg-1, and 1.77%, respectively. The major heavy metals were Cd, Cu, Zn, Hg, and Pb, which were 3.73, 1.50, 1.42, 1.31, and 1.31 times the soil background values for Hebei Province, respectively. The TP and heavy metal (Cd, Cu, Zn, Hg, and Pb) content showed a decreasing trend from the Fuhe River estuary to the downstream Zaolinzhuang, whereas the TN and TOC content showed no marked trends. TN, TP, TOC, and heavy metals (Cd, Cu, Zn, Hg, and Pb) were enriched in surface sediments (0-10 cm). The TP content in the surface sediments (0-10 cm) of the Fuhe River estuary, Fuhe River estuary-Nanliuzhuang, and Nanliuzhuang subareas were heavily polluted; the Wangjiazhai and Guangdian subareas were moderately polluted; and the Zaolinzhuang subarea was slightly polluted. Cd and Hg were the major contributors to heavy metal pollution, which were at considerable risk and moderate risk levels, respectively. The heavy metals in surface sediments (0-10 cm) of the Fuhe River estuary, Fuhe River estuary-Nanliuzhuang, and Nanliuzhuang subareas were at a considerable risk level, and the sediments below 30 cm presented a low risk level. The leaching concentrations of heavy metals in sediments from the subarea of severe ecological risk level were far less than the identification standard values of leaching toxicity, suggesting that the sediments can be treated as general waste after dredging.

Utilization of coal fly ash waste for effective recapture of phosphorus from waters.

Reutilization of the waste by-products from industrial and agricultural activities is crucially important towards attainment of environmental sustainability and the 'circular economy'. In this study, we have developed and evaluated a sustainably-sourced adsorbent from coal fly ash, which was modified by a small amount of lanthanum (La-FA), for the recapture of phosphorous (P) from both synthetic and real natural waters. The prepared La-FA adsorbent possessed typical characteristic diffraction peaks similar to zeolite type Na-P1, and the BET surface area of La-FA was measured to be 10.9 times higher than that of the original FA. Investigation of P adsorption capability indicated that the maximum adsorption (10.8 mg P g-1) was 6.14 times higher than that (1.8 mg P g-1) of the original fly ash material. The ζ potentials measurement and P K-edge X-ray Absorption Near Edge Structure (XANES) spectra demonstrated that P was bonded on La-FA surfaces via an adsorption mechanism. After applying the proposed adsorbent to real lake water with La/P molar ratios in the range from 0.5:1 to 3:1, the La-FA adsorbent showed the highest phosphate removal ability with a La/P molar ratio 1:1, and the P adsorption was similar to that performance with the synthetic solution. Moreover, the La-FA absorbent produced a negligible effect on the concentrations of total dissolved nitrogen (TDN), NH4+-N and NO3--N in water. This study thus provides a potential material for effective P recapture and details of its operation.

Loss of retrograde endocannabinoid signaling and reduced adult neurogenesis in diacylglycerol lipase knock-out mice.

Endocannabinoids (eCBs) function as retrograde signaling molecules at synapses throughout the brain, regulate axonal growth and guidance during development, and drive adult neurogenesis. There remains a lack of genetic evidence as to the identity of the enzyme(s) responsible for the synthesis of eCBs in the brain. Diacylglycerol lipase-alpha (DAGLalpha) and -beta (DAGLbeta) synthesize 2-arachidonoyl-glycerol (2-AG), the most abundant eCB in the brain. However, their respective contribution to this and to eCB signaling has not been tested. In the present study, we show approximately 80% reductions in 2-AG levels in the brain and spinal cord in DAGLalpha(-/-) mice and a 50% reduction in the brain in DAGLbeta(-/-) mice. In contrast, DAGLbeta plays a more important role than DAGLalpha in regulating 2-AG levels in the liver, with a 90% reduction seen in DAGLbeta(-/-) mice. Levels of arachidonic acid decrease in parallel with 2-AG, suggesting that DAGL activity controls the steady-state levels of both lipids. In the hippocampus, the postsynaptic release of an eCB results in the transient suppression of GABA-mediated transmission at inhibitory synapses; we now show that this form of synaptic plasticity is completely lost in DAGLalpha(-/-) animals and relatively unaffected in DAGLbeta(-/-) animals. Finally, we show that the control of adult neurogenesis in the hippocampus and subventricular zone is compromised in the DAGLalpha(-/-) and/or DAGLbeta(-/-) mice. These findings provide the first evidence that DAGLalpha is the major biosynthetic enzyme for 2-AG in the nervous system and reveal an essential role for this enzyme in regulating retrograde synaptic plasticity and adult neurogenesis.

The metabotropic glutamate receptor 7 allosteric modulator AMN082: a monoaminergic agent in disguise?

Metabotropic glutamate receptor 7 (mGluR7) remains the most elusive of the eight known mGluRs primarily because of the limited availability of tool compounds to interrogate its potential therapeutic utility. The discovery of N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN082) as the first orally active, brain-penetrable, mGluR7-selective allosteric agonist by Mitsukawa and colleagues (Proc Natl Acad Sci USA 102:18712-18717, 2005) provides a means to investigate this receptor system directly. AMN082 demonstrates mGluR7 agonist activity in vitro and interestingly has a behavioral profile that supports utility across a broad spectrum of psychiatric disorders including anxiety and depression. The present studies were conducted to extend the in vitro and in vivo characterization of AMN082 by evaluating its pharmacokinetic and metabolite profile. Profiling of AMN082 in rat liver microsomes revealed rapid metabolism (t(1/2) < 1 min) to a major metabolite, N-benzhydrylethane-1,2-diamine (Met-1). In vitro selectivity profiling of Met-1 demonstrated physiologically relevant transporter binding affinity at serotonin transporter (SERT), dopamine transporter (DAT), and norepinephrine transporter (NET) (323, 3020, and 3410 nM, respectively); whereas the parent compound AMN082 had appreciable affinity at NET (1385 nM). AMN082 produced antidepressant-like activity and receptor occupancy at SERT up to 4 h postdose, a time point at which AMN082 is significantly reduced in brain and plasma while the concentration of Met-1 continues to increase in brain. Acute Met-1 administration produced antidepressant-like activity as would be expected from its in vitro profile as a mixed SERT, NET, DAT inhibitor. Taken together, these data suggest that the reported in vivo actions of AMN082 should be interpreted with caution, because they may involve other mechanisms in addition to mGluR7.