Identification of high-concern organic pollutants in tap waters from the Yangtze River in China based on combined screening strategies.

Recently, numerous organic pollutants have been detected in water environment. The safety of our drinking water has attracted widespread attention. Effective methods to screen and identify high-concern substances are urgently needed. In this study, the combined workflow for the detection and identification of high-concern organic chemicals was established and applied to tap water samples from the Yangtze River Basin. The solid phase extraction (SPE) sorbents were compared and evaluated and finally the HLB cartridge was selected as the best one for most of the contaminants. Based on target, suspect and non-target analysis, 3023 chemicals/peaks were detected. Thirteen substances such as diundecyl phthalate (DUP), 2-hydroxyatrazine, dioxoaminopyrine and diethyl-2-phenylacetamide were detected in drinking water in the Yangtze River Basin for the very first time. Based on three kinds of prioritization principles, 49 ubiquitous, 103 characteristic chemicals and 13 inefficiently removed chemicals were selected as high-concern substances. Among them, 8, 31, 9, 3, 4 substances overlapped with the toxic, risky or high-concern chemicals lists in China, America, European Union, Japan, Korea, respectively. Specific management and removal strategies were further recommended. The workflow is efficient for identification of key pollutants.

Identification of Glucocorticoid Receptor Antagonistic Activities and Responsible Compounds in House Dust: Bioaccessibility Should Not Be Ignored.

More and more contaminants in dust have been found to be glucocorticoid receptor (GR) disrupting chemicals. However, little is known about the related potency and responsible toxicants, especially for the main bioaccessible ones in dust. An effect-directed analysis (EDA)-based workflow was developed, including solvent-based exhaustive extraction/tenax-assisted bioaccessible extraction (TBE), high-throughput bioassays, suspect and non-target analysis, as well as in silico candidate selection, for a more realistic identification of responsible contaminants in dust. None of the 39 dust samples from 23 cities in China exhibited GR agonistic activity, while GR antagonistic potencies were detected in 34.8% of samples, being significantly different from the high detection frequency of GR agonistic activities in other environmental media. The GR antagonistic potencies of the dust samples were all reduced after bioaccessible extraction. The mean bioaccessibility of GR antagonistic potency compared with the related exhaustive extracts was 36.8%, and the lowest value was 9%. By using in silico candidate selection, greater than 99% candidate chemical structures which were found by a non-target screening strategy were removed. Di-n-butyl phthalate (DnBP), diisobutyl phthalate (DiBP), and nicotine (NIC) were responsible for the activities of the exhaustive extracts of dust, contributing up to 91% potencies. DiBP and DnBP were also responsible for the bioaccessible activities, contributing up to 79% potencies. However, the contribution from NIC decreased significantly and can be ignored because of its low bioaccessibility. This study suggests that the improved workflow combining extraction, reporter gene bioassays, suspect and non-target analysis, as well as in silico candidate selection is useful for EDA analysis in dust samples. In addition, exhaustive extraction may overestimate the risk of contaminants, while bioaccessibility evaluation based on bioaccessible extraction is essential in both effect evaluation and toxicant identification.

"Three-in-One" Structural-Building-Mode-Based Ti16-Type Titanium Oxo Cluster Entirely Protected by the Ligands Benzoate and Salicylhydroxamate.

Titanium oxo clusters (TOCs) with accurate molecular structures have potential applications in photocatalysis, such as photocatalytic degradation, hydrogen production, and water oxidation. The hydrolytic stability and light absorption ability of TOCs have important impacts on photocatalysis, where the selection of peripheral organic ligands plays a significant role. In this regard, salicylhydroxamic acid (abbreviated as H3L) attracts our attention, acting as a ligand for its multidentate and dye-functional features, which can increase the hydrolytic stability and broaden light absorption for TOCs. Herein, two TOCs were solvothermally synthesized and structurally characterized using H3L, formulated as [Ti8(µ2-O)2(µ3-O)2(OiPr)12(L)4]·2CH3CN (1) and [Ti16(µ2-O)10(µ3-O)4(PhCOO)14(L)6(HL)2]·4CH3CN·2iPrOH (2). Complex 2 was obtained by adding excessive benzoic acid over the reaction system of 1, resulting in enhanced hydrolytic stability via the replacement of all alkoxy ligands by multidentate ligands for protection. Interestingly, for the first time, the "three-in-one" structural building mode with {Ti6} + {Ti4} + {Ti6} by the common subunits in 2 was observed among all reported TOCs. Moreover, complex 2 can strongly absorb visible light reaching up to 700 nm and exhibit obvious activity for the photodegradation of methyl orange.

Effect-Directed Analysis Based on the Reduced Human Transcriptome (RHT) to Identify Organic Contaminants in Source and Tap Waters along the Yangtze River.

Since a large number of contaminants are detected in source waters (SWs) and tap waters (TWs), it is important to perform a comprehensive effect evaluation and key contributor identification. A reduced human transcriptome (RHT)-based effect-directed analysis, which consisted of a concentration-dependent RHT to reveal the comprehensive effects and noteworthy pathways and systematic identification of key contributors based on the interactions between compounds and pathway effects, was developed and applied to typical SWs and TWs along the Yangtze River. By RHT, 42% more differentially expressed genes and 33% more pathways were identified in the middle and lower reaches, indicating heavier pollution. Hormone and immune pathways were prioritized based on the detection frequency, sensitivity, and removal efficiency, among which the estrogen receptor pathway was the most noteworthy. Consistent with RHT, estrogenic effects were widespread along the Yangtze River based on in vitro evaluations. Furthermore, 38 of 100 targets, 39 pathway-related suspects, and 16 estrogenic nontargets were systematically identified. Among them, diethylstilbestrol was the dominant contributor, with the estradiol equivalent (EEQ) significantly correlated with EEQwater. In addition, zearalenone and niclosamide explained up to 54% of the EEQwater. The RHT-based EDA method could support the effect evaluation, contributor identification, and risk management of micropolluted waters.

Mechanism of lncRNA H19 in Regulating Pulmonary Injury in Hyperoxia-Induced Bronchopulmonary Dysplasia Newborn Mice.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) is a pulmonary injury related to inflammation and is a major cause of premature infant death. Long noncoding RNAs (lncRNAs) are important regulators in pulmonary injury and inflammation. We investigated the molecular mechanism of lncRNA H19 in pulmonary injury and inflammation in hyperoxia (Hyp)-induced BPD mice. STUDY DESIGN: The BPD newborn mouse model was established and intervened with H19 to evaluate the pathologic conditions and radial alveolar count (RAC) in lung tissues of mice in the room air (RA) and Hyp group on the 4th, 7th, and 14th days after birth. The levels of BPD-related biomarkers vascular endothelial growth factor (VEGF), transforming growth factor ß1 (TGF-ß1), and surfactant protein C (SPC) in lung tissues were detected on the 14th day after birth. The expression of and relationships among H19 and miR-17, miR-17, and STAT3 were detected and verified. Levels of interleukin (IL)-6, IL-1ß, p-STAT3, and STAT3 levels in mouse lung tissues were detected on the 14th day after birth. RESULTS: Hyp-induced mice showed increased alveolar diameter, septum, and hyperemia and inflammatory cell infiltration, upregulated H19, decreased overall number and significantly reduced RAC on the 7th and 14th days after birth, which were reversed in the si-H19-treated mice. VEGF was upregulated and TGF-ß1 and SPC was decreased in si-H19-treated mice. Moreover, H19 competitively bound to miR-17 to upregulate STAT3. IL-6 and IL-1ß expressions and p-STAT3 and STAT3 levels were downregulated after inhibition of H19. CONCLUSION: Downregulated lncRNA H19 relieved pulmonary injury via targeting miR-17 to downregulate STAT3 and reduced inflammatory response caused by p-STAT3 in BPD newborn mice. KEY POINTS: · lncRNA H19 was highly expressed in Hyp-induced BPD newborn mice.. · si-H19 relieved pulmonary injury in Hyp-induced BPD newborn mice.. · si-H19 upregulated miR-17 and downregulated STAT3 expression..

Overexpression of Long Noncoding RNA H19 Inhibits Cardiomyocyte Apoptosis in Neonatal Rats with Hypoxic-Ischemic Brain Damage Through the miR-149-5p/LIF/PI3K/Akt Axis.

Hypoxic-ischemic brain damage (HIBD) is a leading cause of fatality and neural system injury in neonates. This study aims to explore the effect of long noncoding RNA H19 on cardiomyocyte apoptosis in neonatal rats with HIBD. The neonatal rat model of HIBD was established. The cerebral infarction volume and apoptosis index of cardiomyocyte increased, while H19 expression decreased in neonatal rats with HIBD. After the lentivirus vector of overexpressed H19 was injected into neonatal rats with HIBD, the cardiomyocyte apoptosis was suppressed; levels of inflammatory factors and oxidative stress injury of myocardial tissues were reduced. The binding relationships between H19 and miR-149-5p, and miR-149-5p and leukemia inhibitory factor (LIF) were predicted by a bioinformatics website and verified using the dual-luciferase reporter gene assay. H19 competitively bound to miR-149-5p to upregulate LIF expression and activate the PI3K/Akt pathway. Moreover, a functional rescue experiment was carried out. Injection of Wortmannin reversed the inhibitory effect of H19 overexpression on cardiomyocyte apoptosis in neonatal rats with HIBD. It could be concluded that H19 competitively bound to miR-149-5p to upregulate LIF expression and activate the PI3K/Akt pathway, thus reducing cardiomyocyte apoptosis in neonatal rats with HIBD. This study may offer new insights for HIBD treatment.

Effect of Hf doping on He behavior in tritium storage material ZrCo.

An exhaustive analysis based on density functional theory (DFT) simulations of the effect of Hf doping on helium behavior has been performed in ZrCo. The He impurities have been placed both at interstitial positions and substitutional positions from the first nearest neighbor (1nn) of the Hf atom to the sixth nearest neighbor (6nn). In such areas, the electronic charge density is different, and therefore the formation and diffusion of He atoms vary in the surrounding of the Hf atom. The results show that Hf doping reduces the volume of the interstitial sites nearby, resulting in the weakening ability of the interstitial sites to accommodate He atoms. According to the results of formation energy, whether it is the substitutional He or the interstitial He atom, the formation is not only related to the distance of Hf, but more importantly, it is closely related to the unit cell where the He atom is located. In addition, Hf atoms promote the capture of He atoms by vacancies nearby and the migration of He atoms between the tetrahedral positions. The result also validates the well-known knowledge of vacancies as efficient sinks for He atoms in ZrCo. From the lower and lower migration energetic barriers along 3nn → 2nn → 1nn → 1nn pathways, we can infer an increasing mobility of the He atom from 3nn to 1nn. This situation could favor their accumulation surrounding an Hf atom, improving the ability of helium retention. These findings provide really indisputable evidence that the Hf dopant makes a difference in the behavior of He atoms in bulk ZrCo. Therefore, a ZrCo system with Hf doping can be considered as a good candidate for tritium storage material in a future nuclear fusion reactor.

Cross-Model Comparison of Transcriptomic Dose-Response of Short-Chain Chlorinated Paraffins.

Short-chain chlorinated paraffins (SCCPs) have attracted attention because of their toxicological potential in humans and wildlife at environmentally relevant doses. However, limited information is available regarding mechanistic differences across species in terms of the biological pathways that are impacted by SCCP exposure. Here, a concentration-dependent reduced human transcriptome (RHT) approach was conducted to evaluate 15 SCCPs in HepG2 cells and compared with our previous results using a reduced zebrafish transcriptome (RZT) approach in zebrafish embryos (ZFEs). Generally, SCCPs induced a broader suite of biological pathways in ZFEs than HepG2 cells, and all of the 15 SCCPs were more potent in HepG2 cells compared to ZFEs. Despite these general differences, the transcriptional potency of SCCPs in both model systems showed a significant linear relationship (p = 0.0017, r2 = 0.57), and the average ratios of transcriptional potency for each SCCP in RZT to that in RHT were ∼100,000. C10H14Cl8 was the most potent SCCP, while C10H17Cl5 was the least potent in both ZFEs and HepG2 cells. An adverse outcome pathway network-based analysis demonstrated model-specific responses, such as xenobiotic metabolism that may be mediated by different nuclear receptor-mediated pathways between HepG2 cells (e.g., CAR and AhR activation) and ZFEs (e.g., PXR activation). Moreover, induced transcriptional changes in ZFEs associated with pathways and molecular initiating events (e.g., activation of nicotinic acetylcholine receptor) suggest that SCCPs may disrupt neural development processes. The cross-model comparison of concentration-dependent transcriptomics represents a promising approach to assess and prioritize SCCPs.

Facilitators and challenges experienced by nursing homes enrolling in the CDC national health care safety network.

BACKGROUND: Standardized measurement of health care-associated infections is essential to improving nursing home (NH) resident safety, however voluntary enrollment of NHs in Centers for Disease Control and Prevention's National Healthcare Safety Network (NHSN) requires several steps. We sought to prospectively identify NH structural, process or staff characteristics that affect enrollment and data submission among a cohort of NHs receiving facilitated implementation. METHODS: The evaluation employed a mixed methods approach. The meta-theoretical Consolidated Framework for Implementation Research was used to analyze reported facilitators and challenges. Primary and secondary outcomes were time to NHSN enrollment and data submission, respectively. RESULTS: Of 36 participating NHs, 27 (75%) completed NHSN enrollment and 21 (58%) submitted 1 or more months of infection data during the 8-month study period. Mean days to complete enrollment was 82 (standard deviation [SD] = 24, range = 51-139) and days to first data submission was 112 (SD = 45, range = 71-245). Characteristics of NH staff liaisons associated with shorter time to enrollment included infection prevention and control knowledge, personal confidence, and responsibility for infection prevention and control activities. Facility characteristics were not associated with outcomes. DISCUSSION: Time to NHSN enrollment and submission related more to characteristics of the person leading the process than to characteristics of the NH. CONCLUSIONS: External partnerships that provide real-time support and resources are important assets in promoting successful NH participation in NHSN.

Referrals of Infection Control Breaches to Public Health Authorities: Ambulatory Care Settings Experience, 2017.

BACKGROUND: Beginning in October 2016, the Centers for Medicare & Medicaid Services (CMS) issued expanded guidance requiring accrediting organizations and state survey agencies to report serious infection control breaches to relevant state health departments. This project sought to characterize and summarize The Joint Commission's early experiences and findings in applying this guidance to facilities accredited under the ambulatory and office-based surgery programs in 2017. METHODS: Surveyor notes were retrospectively reviewed to identify individual breaches, and then the Centers for Disease Control and Prevention's Infection Prevention Checklist for Outpatient Settings was used to categorize and code documented breaches. RESULTS: Of 845 ambulatory organizations, 39 (4.6%) had breaches observed during the survey process and reported to health departments. Within these organizations, surveyors documented 356 breaches, representing 52 different breach codes. Common breach domains were sterilization of reusable devices, device reprocessing observation, device reprocessing, disinfection of reusable devices, and infection control program and infrastructure. Eight of the 39 facilities (20.5%) were cited for not performing the minimum level of reprocessing based on the items' intended use, reusing single-use devices, and/or not using aseptic technique to prepare injections. CONCLUSION: The CMS infection control breach reporting requirement has helped highlight some of the challenges faced by ambulatory facilities in providing a safe care environment for their patients. This analysis identified numerous opportunities for improved staff training and competencies as well as leadership oversight and investment in necessary resources. More systematic assessments of infection control practices, extending to both accredited and nonaccredited ambulatory facilities, are needed to inform oversight and prevention efforts.

Papaya CpbHLH1/2 regulate carotenoid biosynthesis-related genes during papaya fruit ripening.

The ripening of papaya is a physiological and metabolic process associated with accumulation of carotenoids, alternation of flesh color and flavor, which depending on genotype and external factors such as light and hormone. Transcription factors regulating carotenoid biosynthesis have not been analyzed during papaya fruit ripening. RNA-Seq experiments were implemented using different ripening stages of papaya fruit from two papaya varieties. Cis-elements in lycopene ß-cyclase genes (CpCYC-B and CpLCY-B) were identified, and followed by genome-wide analysis to identify transcription factors binding to these cis-elements, resulting in the identification of CpbHLH1 and CpbHLH2, two bHLH genes. The expressions of CpbHLH1/2 were changed during fruit development, coupled with transcript increase of carotenoid biosynthesis-related genes including CpCYC-B, CpLCY-B, CpPDS2, CpZDS, CpLCY-E, and CpCHY-B. Yeast one-hybrid (Y1H) and transient expression assay revealed that CpbHLH1/2 could bind to the promoters of CpCYC-B and CpLCY-B, and regulate their transcriptions. In response to strong light, the results of elevated expression of carotenoid biosynthesis-related genes and the changed expression of CpbHLH1/2 indicated that CpbHLH1/2 were involved in light-mediated mechanisms of regulating critical genes in the carotenoid biosynthesis pathway. Collectively, our findings demonstrated several TF family members participating in the regulation of carotenoid genes and proved that CpbHLH1 and CpbHLH2 individually regulated the transcription of lycopene ß-cyclase genes (CpCYC-B and CpLCY-B). This study yielded novel findings on regulatory mechanism of carotenoid biosynthesis during papaya fruit ripening.

Syntheses, crystal-solution structures and magnetic properties of a series of decanuclear heterometallic [LnCoCo] (Ln = Eu, Gd, Tb, Dy) clusters.

Four unprecedented decanuclear heterometallic [Ln2CoII4CoIII4] clusters based on a diethanolamine ligand (H2dea), namely [Eu2CoII4CoIII4(dea)8(HCOO)4(OH)2(Cl)2(CH3OH)2]Cl2·4CH3OH·2H2O (1), [Gd2CoII4CoIII4(dea)8(HCOO)4(OH)2(Cl)2(CH3OH)2]Cl2·4CH3OH·2H2O (2), [Tb2CoII4CoIII4(dea)8(HCOO)4(OH)2(Cl)2(CH3OH)2]Cl2·2CH3OH·4H2O (3) and [Dy2CoII4CoIII4(dea)8(HCOO)4(OH)2(Cl)2(CH3OH)2]Cl2·2CH3OH·4H2O (4) were synthesized through a facile solution method. Single-crystal X-ray diffraction analyses reveal that complexes 1-4 consist of a [Ln2CoII4CoIII4] core, which is constructed by bridging a quasi-double cuboidal [Ln2CoII2CoIII2] core with two [CoIICoIII] units. Electrospray ionization mass spectrometry (ESI-MS) using methanol solution reveals that complexes 1-4 are stable in the solution, and the clusters undergo three different substitution reactions (Cl- replaced by OH-, OH- replaced by CH3O- and HCOO- replaced by OH-/CH3O-) at the same time in the ionization state. Magnetic susceptibilities reveal ferromagnetic couplings within complexes 3 and 4, and the magnetocaloric effect (MCE) for 2 was also evaluated and the maximum entropy change (-ΔSm) value reaches 16.3 J kg-1 K-1 at about 3 K and 5 T.

Structure elucidation and immunological activity of a novel glycopeptide from mannatide.

A water-soluble glycopeptide, designated as MTW, was isolated and purified from crude mannatide by DEAE-Sepharose. MTW showed one symmetrical peak on HPGPC with an average molecular weight of 2.95×104Da. MTW contained 16 kinds of amino acids and the total amino acid content was 0.95%. The structure of polysaccharide moiety of MTW was elucidated based on monosaccharide composition, methylation analysis, partial acid hydrolysis, IR and 1D/2D NMR spectroscopy. The results showed that MTW was a homogeneous glycopeptide including mannose and glucose with a molar ratio of 2:1. The polysaccharide moiety of MTW had a backbone of (1→6)-α-d-Man p residues, which highly branched at O-2 position of (1→2,6)-α-d-Man p residues. The side chains were mainly composed of (1→)-α-d-Man p, (1→2)-α-d-Man p, (1→4)-α-d-Glc p, (1→4,6)-α-d-Glc p residues. The backbone of the polysaccharide moiety of MTW was the same as MT2-A (Li et al. [1]), which was the main component of mannatide, but the side chains of MTW were somewhat different from that of MT2-A. Complement-fixation test indicated that MTW had the same beneficial effect on immunological activity as MT2-A.

Constructing three-dimensional (3D) nanocrystalline models of Li4SiO4 for numerical modeling and simulation.

The three-dimensional (3D) nanocrystalline models of lithium silicates with the log-normal grain size distribution are constructed by constrained Voronoi tessellation. During evolution process, the algorithm is improved. We proposed a new algorithm idea by combining Genetic Algorithm (GA) with Least Square (LS) method to make up for the disadvantages of traditional genetic algorithm which may be easily trapped in local optimal solution. In the process of modeling, it is the first time, to the best of our knowledge, that we keep the whole sample showing the charge neutrality by deleting the excess atoms on the polyhedron boundary during the modeling. By using the molecular-dynamics method, the relaxation procedure of nanostructured Li4SiO4 is carried out. The results show that the average mass density of the sample is slightly lower than the experimental data of the perfect crystal after relaxation process. In addition, boundary component proportion (BCP) and density reduction proportion (DRP) of the sample is obtained, respectively. The present results display a significantly reduced BCP but an increased DRP when increasing the mean grain size of the sample.

Enhanced proliferation and defective activation-induced cell death of CD4+ T cells in childhood asthma.

BACKGROUND: Hyperactivation of CD4+ T cells in peripheral blood and airway tissues has been suggested to play a key role in the development and maintenance of chronic inflammation in childhood asthma. However, the underlying mechanisms are not yet clear. OBJECTIVE: To investigate alterations in serum levels of T helper cell-related cytokines, mitogen-stimulated CD4+ T cell proliferation and activation-induced cell death (AICD) in childhood asthma. METHODS: 21 children with untreated asthma and 21 healthy volunteers (age and gender matched) participated in this study. Th1/Th2/Th17 cytokines in serum were analyzed by flow cytometry. CD4+ T cells were isolated from participants by using immuno-magnetic beads and were stimulated by phytohemagglutinin (PHA). Cell proliferation was evaluated with a Cell Counting Kit-8 (CCK-8). Activation induced cell death (AICD) of CD4+ T cells was also induced by PHA and apoptosis was assayed by annexin V/PI staining. Quantitative RT-PCR was carried out to analyze Fas and FasL mRNA expression. FLIPL, caspase-8 and Bcl-2 were detected by western blot analysis. RESULTS: In children with asthma, the proliferative capacity of CD4+ T cells was enhanced and AICD was inhibited significantly, while serum IL-4, IL-10 and TNF were markedly higher compared with the control group. Fas mRNA expression in the asthma group was obviously lower than that in the control group, while no change was detected in FasL mRNA expression. Western blot analysis showed that the levels of the anti-apoptotic proteins, FLIPL and Bcl-2 in CD4+ T cells of the asthma group were significantly higher than in the control group. Spearman's correlation tests showed that only IL-4 correlated positively with FLIPL and Bcl-2 expression, while IL-10 and TNF were unrelated to FLIPL and Bcl-2 expression. CONCLUSIONS: These results indicate that enhanced proliferation and defective AICD of CD4+ T cells influence the T cell-mediated inflammatory reaction in childhood asthma and that increased IL-4, FLIPL and Bcl-2 expression and decreased Fas expression jointly participate in these changes in cell proliferation and apoptosis.ression and decreased Fas expression jointly participate in these changes in cell proliferation and apoptosis.

Effects of nanoscale zero-valent iron particles on biological nitrogen and phosphorus removal and microorganisms in activated sludge.

The use of nanoscale zero-valent iron (NZVI) particles in environmental remediation and wastewater treatment has recently increased. The effects of NZVI on nitrogen and phosphorus removal were examined under continuous aerobic/anaerobic conditions by employing activated sludge. NZVI did not display any measurable effect on nitrogen removal at the concentration of 50mg/L and below. However, 200mg/L of NZVI inhibited NH4(+)-N removal. The addition of NZVI at 20mg/L and above significantly (p<0.05) improved the phosphorous removal. The microbial activities were inhibited upon exposure to NZVI according to the ATP and reactive oxygen species (ROS) results. In comparison to control, the ATP content decreased by around 13%, 31% and 43% at the NZVI doses of 20, 50, and 200mg/L, respectively, probably due to ROS production under NZVI exposure. Lactate dehydrogenase (LDH) release assay suggested that NZVI concentration of 200mg/L cast adverse effects on microorganisms. Interestingly, lower concentrations of NZVI (20 and 50mg/L) boosted the dehydrogenase activity; however, approximately 19% depression in dehydrogenase activity was detected at 200mg/L. The high throughput 16S rDNA pyrosequencing results indicated that uncultured bacterial genera Sinobacteraceae, Xanthomonadaceae, Alcaligenaceae and Propionivibrio were sensitive to NZVI particles.

Design, synthesis and evaluation of 7-azaindazolyl-indolyl-maleimides as glycogen synthase kinase-3ß (GSK-3ß) inhibitors.

A series of 7-azaindazolyl-indolyl-maleimides were designed, synthesized and evaluated for their GSK-3ß inhibitory activity. Most compounds exhibited potent activity against GSK-3ß. Among them, compounds 17a, 17b, 17g, 17i, 29a and 30 significantly reduced Aß-induced Tau hyperphosphorylation, showin;g the inhibition of GSK-3ß at the cell level. Preliminary structure-activity relationships were discussed based on the experimental data obtained.

Design, synthesis, and biological evaluation of acetophenone derivatives as dual binding acetylcholinesterase inhibitors.

As part of a project aimed at developing new agents for potential application in Alzheimer's disease, a new series of acetophenone derivatives which possess alkylamine side chains were designed, synthesized and assayed as acetylcholinesterase (AChE) inhibitors that could simultaneously bind to the peripheral and catalytic sites of the enzyme. The compounds were synthesized, and the inhibitory activities toward AChE and butyrylcholinesterase (BuChE) in vitro were determined using a modified Ellman method. Of the compounds tested, 6 derivatives were found to inhibit AChE in the micromolar range. The best compound, 2e, had an 1C50 of 0.13 microM. A detailed molecular modeling study was performed to explore the interaction of 2e with AChE.

Phosphate removal from aqueous solutions by nanoscale zero-valent iron.

In this study, nanoscale zero-valent iron (NZVI) was synthesized by conventional liquid-phase chemical reduction methods without a support material and then characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM) and X-ray diffraction (XRD). The effect of NZVI particles on phosphate removal from aqueous solutions was examined. The results showed that the phosphate removal efficiency increased from 34.49% to 87.01% as the dosage of nanoscale iron particles increased from 100 to 600 mg L(-1) with an initial phosphate concentration of 10 mg L(-1), and the phosphate removal efficiency decreased from 72.89% to 51.39% as the initial phosphate concentration increased from 10 to 90 mg L(-1), with 400 mg L(-1) NZVI. Phosphate removal efficiencies of 99.41% and 95.09% were achieved at pH values of 2 and 4, respectively, with an initial phosphate concentration of 20 mg L(-1) and 400mg L(-1) NZVI. The use of NZVI particles synthesized in a carboxymethyl cellulose (CMC)-water solution significantly enhanced phosphate removal from an aqueous solution compared with the use of NZVI synthesized in an ethanol-water solution. NZVI particles achieved 71.34% phosphate removal, which was remarkably higher than that of microscale zero-valent iron (MZVI) particles (16.35%) with 10 mg L(-1) of phosphate and 400mg L(-1) iron. Based on the removal mechanism analysis performed in this study, we recommend that phosphate removal be accomplished by simultaneous adsorption and chemical precipitation. The XRD patterns of the NZVI before and after the reactions indicated the formation of crystalline vivianite (Fe3(PO4)2 x 8H2O) during the procedure.