Intermediate Toxicity Research Articles

Sunlight driven photolytic ozonation as an advanced oxidation process in the oxidation of bezafibrate, cotinine and iopamidol

This study investigates the efficacy of the system O3/sunlight radiation compared to dark ozonation when treating pharmaceuticals compounds of different reactivity, namely bezafibrate, cotinine, and iopamidol. Results show the beneficial effects of simulated sunlight radiation (300–800 nm) when treating ozone recalcitrant compounds such as cotinine and iopamidol. The system O3/sunlight radiation increased mineralization extent in all cases if compared to dark ozonation. Transformation products identified in individual runs suggest that amine oxidation and further alkyl chain attack is the main route of bezafibrate ozonation. Hydroxylation seems to be the preferential path in cotinine abatement while H abstraction from alcoholic moieties is suggested in the case of iopamidol. Toxicity of intermediates was approximately evaluated by QSAR methodologies and experimentally through Daphnia Magna survival after 24 h. As a rule of thumb, initial intermediates generated are even more toxic than parent compounds, however, after 120 min of treatment, toxicity significantly decreased. Amongst the most toxic compounds generated: 4-Chlorobenzoyltyramine, and 4-Chloro-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-benzamide (from bezafibrate), and N-(2-Hydroxy-1-hydroxymethyl-ethyl)-N'-(1-hydroxymethyl-2-oxo-ethyl)-5-(2-hydroxy-propionylamino)-2,4,6-triiodo-isophthalamide, N,N′-Bis-(1-hydroxymethyl-2-oxo-ethyl)-5-(2-hydroxy-propionylamino)-2,4,6-triiodo-isophthalamide, and N-(1-Hydroxymethyl-2-oxo-ethyl)-5-(2-hydroxy-propionylamino)-2,4,6-triiodo-isophthalamide (from iopamidol) were identified.

Toxicity of aromatic pollutants and photooxidative intermediates in water: A QSAR study

Extensive commercial use of aromatic hydrocarbons results with significant amounts of these chemicals and related by-products in waters, causing a severe ecological and health threat, thus requiring an increased attention.This study was aimed at developing models for prediction of the initial toxicity of the aromatic water-pollutants (expressed as EC50 and TU0) as well as the toxicity of their intermediates at half-life of the parent pollutant (TU1/2). For that purpose, toxicity toward Vibrio fischery was determined for 36 single-benzene ring compounds (S-BRCs), diversified by the type, number and position of substituents. Quantitative structure-activity relationship (QSAR) methodology paired with genetic algorithm optimization tool and multiple linear regression was applied to obtain the models predicting the targeted toxicity, which are based on pure structural characteristics of the tested pollutants, avoiding thus additional experimentation. Upon derivation of the models and extensive analysis on training and test sets, 4-, 4- and 5-variable models (for EC50 and TU0, TU1/2, respectively) were selected as the most predictive possessing 0.839<R2< 0.901 and 0.789<Q2< 0.859. The analysis of the selected descriptors indicated three major structural characteristics influencing the toxicity: electronegativity, geometry and electrotopological states of the molecule. Degradation kinetics determining as well the pathways of intermediates formation, reflected over ionization potential, was found to be an important parameter determining the toxicity in half-life.

Cytotoxicity of layered metal phosphorus chalcogenides (MPXY) nanoflakes; FePS3, CoPS3, NiPS3

Metal phosphorus chalcogenides is a new class of 2D materials that have shown interesting semiconducting, electronic, anisotropic, magnetic, dielectric, structural and optical properties. Recently, NiPS3, FePS3 and CoPS3 in particular have been highlighted for promising potential in important energy applications such as electrocatalysts for water splitting and hydrogen storage. However, little is known about the toxicological hazards that they may pose on humans. Here, we investigated the cytotoxicity of NiPS3, FePS3 and CoPS3 on human lung carcinoma cells (A549) and normal human bronchial cells (BEAS-2B) to address this concern. Upon treatment of these cells with different MPXY materials, we determined the remaining cell viability using water soluble tetrazolium salt (WST-8) assay. We found that CoPS3 was most toxic followed by FePS3 with intermediate toxicity while NiPS3 showed the lowest toxicity among the three materials tested for both cell lines. When viewed with other layered materials, these MPXY samples present comparable toxicities with transition metal dichalcogenides and black phosphorus at low concentrations.

Decolorization of Reactive Orange 122 as an Organic Pollutant by the Sonoelectrochemical Process and Toxicity Evaluation

Introduction: Combined of electrochemistry and ultrasound (sonoelectrochemistry) is one of the advanced oxidation processes (AOPs) for decolorization of color wastewaters. The physicochemical effects of ultrasound improve the electrooxidation of dye solution and decolorization rate. Materials and Methods: In this study, the decolorization of Reactive Orange 122 (RO122) as an organic pollutant by sonoelectrochemistry has been examined. In this context, the effect of several factors such as hydrogen peroxide concentration, the pH of solution, colour concentration, and the input voltage on decolorization of colourful solution as a single factor were studied. Based on the results, the optimum hydrogen peroxide concentration for removing the colour with the concentration of 10 mgL-1 at 90 minutes was 3.0 mgL-1, with pH about 7.0 and the input potential 1.05 V, the process was carried out without the use of hydrogen peroxide as a discussion parameter at 90 minutes. Results: The results revealed that decolourization and removal of chemical oxygen demand (COD) of both methods were 99% and 70% in the presence of hydrogen peroxide and 97% and 95.5% in the absence of hydrogen peroxide, respectively. Conclusions: Microbial toxicity test assessed the toxicity of intermediates produced during these two procedures, the results indicated, in the absence of hydrogen peroxide, Pseudomonas aeruginosa bacteria showed better performance on the colour of sonoelectrochemical treatment solutions compared to the initial colour of the solution, due to absence of toxic materials from the redistribution of RO122 colour.

H&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt;O&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt; regulates the production of reactive oxygen species in TiO&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt; system and the degradation process of pentachlorophenol

The titanium dioxide photocatalytic oxidation technology of pentachlorophenol (PCP) has attracted widespread attention because of its high degradation efficiency and low toxicity. How to reasonably regulate the production of highly toxic intermediates during the degradation of PCP is currently the hotspot. The photocatalytic degradation of PCP is closely related to the production of reactive oxygen species (ROS). This article studied the effect of H2O2 addition on the production of ROS including •OH, O2•− and H2O2 in three different types of TiO2 photocatalytic systems and their effects on the degradation efficiency of PCP. The results showed that after H2O2 was added, the amount of three kinds of ROS produced by the P25 solution increased, and the degradation rate k of PCP increased. The anatase TiO2 solution produced less •OH, but more O2•− and H2O2 after H2O2 was added. The amount of three kinds of ROS produced by the rutile TiO2 solution increased, and the degradation rate of PCP increased by 50 times. The effects of three kinds of TiO2/H2O2 systems on the photocatalytic degradation of PCP and its intermediate acute toxicity were identified by high performance liquid chromatography and luminescence inhibition. The results showed that there were no highly toxic intermediate products such as tetrachloro-1,4-benzoquinone during the degradation process, and the acute toxicity during degradation was significantly reduced. These results indicated that the addition of H2O2 can regulate the ROS production and PCP degradation process in TiO2 photocatalytic system, and significantly reduced the acute toxicity during the degradation of PCP.

In situ growth of Ag-SnO2 quantum dots on silver phosphate for photocatalytic degradation of carbamazepine: Performance, mechanism and intermediates toxicity assessment

The occurrence of carbamazepine (CBZ) in environments poses a potential risk to aquatic life and exhibits growth inhibition of human embryonic cells. In this work, for the first time a series of Ag-SnO2 quantum dots (QDs)/silver phosphate (AgSn/AgP) composites were synthesized and used as photocatalysts for CBZ degradation. The obtained AgSn/AgP composites showed superior photodegradation efficiency for CBZ removal. The degradation rate constant of 10AgSn/AgP (with 10 wt% of Ag-SnO2 QDs) was almost 8.5, 5.7, 5.7, and 1.9 times as that of Ag-SnO2 QDs, Ag3PO4, Ag/Ag3PO4, and SnO2 QDs/Ag3PO4, respectively. The improved photocatalytic activity could be primarily ascribed to the improved charge separation through a collaborative effect of Ag-SnO2 QDs and Ag3PO4, and in situ photoreduced metallic silver. Electron spin resonance (ESR) measurement and radical trapping experiments suggested that holes (h+), (superoxideradical) ·O2− and (hydroxylradical) ·OH corporately participated in the decomposition of CBZ. Moreover, a reasonable mechanism for photocatalytic degradation of CBZ over 10AgSn/AgP composites was tentatively proposed. Additionally, eight degradation intermediates were determined by liquid chromatography-mass spectrometry (LC-MS). Toxicity evaluation using the Ecological Structure Activity Relationships (ECOSAR) program revealed that the toxicity of most photodegradation intermediates were much lower than that of the parent compound CBZ. This work not only provides a new technique for preparing Ag3PO4-based photocatalysts with high activity, but also demonstrates that 10AgSn/AgP could be a promising photocatalyst for treating water and wastewaters containing CBZ.

Degradation of sulfonamide antibiotics and their intermediates toxicity in an aeration-assisted non-thermal plasma while treating strong wastewater

Aeration-assisted non-thermal plasma (NTP) process is known as promising due to simultaneous generation of oxygen- and nitrogen-based reactive chemicals for non-biodegradable pollutants removal in a wastewater. Despite its effective oxidizing capability, the decomposition mechanism of antibiotics is not yet clarified well. This study verifies the NTP's removal potential of non-biodegradable sulfonamide antibiotics in the treatment of strong wastewater. The instantaneous production of hydrogen peroxide (H2O2) was quantified to prove synergistic advanced oxidation, and degradation kinetic coefficients of N, N-Dimethyl-4-nitrosoaniline (RNO) reveals rapid oxidation rate of NTP. Also, the results of an acute-toxicity test using Daphnia magna demonstrate how the toxicity of antibiotics intermediates responds to the NTP. Results indicate that the NTP has better potential than conventional oxidation processes in terms of OH-radical generation due to the interplay of reactive species. This study provides useful information that aeration-assisted NTP application to wastewater treatment can be a viable option to enhance treatment efficiency via plasma-related reactive species and that how environmental ecotoxicity responds to the by-products of sulfonamide antibiotics.

Immobilization of Planococcus sp. S5 Strain on the Loofah Sponge and Its Application in Naproxen Removal

Planococcus sp. S5, a Gram-positive bacterium isolated from the activated sludge is known to degrade naproxen in the presence of an additional carbon source. Due to the possible toxicity of naproxen and intermediates of its degradation, the whole cells of S5 strain were immobilized onto loofah sponge. The immobilized cells degraded 6, 9, 12 or 15 mg/L of naproxen faster than the free cells. Planococcus sp. cells immobilized onto the loofah sponge were able to degrade naproxen efficiently for 55 days without significant damage and disintegration of the carrier. Analysis of the activity of enzymes involved in naproxen degradation showed that stabilization of S5 cells in exopolysaccharide (EPS) resulted in a significant increase of their activity. Changes in the structure of biofilm formed on the loofah sponge cubes during degradation of naproxen were observed. Developed biocatalyst system showed high resistance to naproxen and its intermediates and degraded higher concentrations of the drug in comparison to the free cells.

Evaluating tetracycline degradation pathway and intermediate toxicity during the electrochemical oxidation over a Ti/Ti4O7 anode

Tetracycline (TC) is one of the most widely used antibiotics with significant impacts on human health and thus it needs appropriate approaches for its removal. In the present study, we evaluated the performance and complete pathway of the TC electrochemical oxidation on a Ti/Ti4O7 anode prepared by plasma spraying. Morphological data and composition analysis indicated a compact coating layer on the anode, which had the characteristic peaks of Ti4O7 as active constituent. The TC electrochemical oxidation on the Ti/Ti4O7 anode followed a pseudo-first-order kinetics, and the TC removal efficiency reached 95.8% in 40 min. The influential factors on TC decay kinetics included current density, anode-cathode distance and initial TC concentration. This anode also had high durability and the TC removal efficiency was maintained over 95% after five times reuse. For the first time, we unraveled the complete pathway of the TC electrochemical oxidation using high-performance liquid chromatograph (HPLC) and gas chromatograph (GC) coupled with mass spectrometer (MS). ·OH radicals produced from electrochemical oxidation attack the double bond, phenolic group and amine group of TC, forming a primary intermediate (m/z = 461), secondary intermediates (m/z = 432, 477 and 509) and tertiary intermediates (m/z = 480, 448 and 525). The latter were further oxidized to the key downstream intermediate (m/z = 496), followed by further downstream intermediates (m/z = 451, 412, 396, 367, 351, 298 and 253) and eventually short-chain carboxylic acids. We also evaluated the toxicity change during the electrochemical oxidation process with bioluminescent bacteria. The bioluminescence inhibition ratio peaked at 10 min (55.41%), likely owing to the high toxicity of intermediates with m/z = 461, 432 and 477 as obtained from quantitative structure activity relationship (QSAR) analysis. The bioluminescence inhibition ratio eventually decreased to 16.78% in 40 min due to further transformation of TC and intermediates. By comprehensively analyzing the influential factors and complete degradation pathway of TC electrochemical oxidation on the Ti/Ti4O7 anode, our research provides deeper insights into the risk assessment of intermediates and their toxicity, assigning new perspectives for practical electrochemical oxidation to effectively eliminate the amount and toxicity of TC and other antibiotics in wastewater.

The different paths and potential risks of photo(-electro)-catalytic degradation for rhodamine B in water by graphene/TiO2 membrane.

The graphene (GR)/TiO2 membrane was prepared by the sol-gel method and coated on the indium tin oxide (ITO) conductive glass, which showed high and stable photo(-electro)-catalytic activities to rhodamine B (Rh-B) in water. Characterization results showed that the GR was dispersed and wrapped in the needle-like TiO2. With GR/TiO2 membrane and simulated sunlight irradiation, the removal efficiency of Rh-B (10mgl-1 and pH at 5.4) arrived at 87.6% within 300min. However, the higher removal efficiency for Rh-B reached to 97.8% by the photo-electro-catalytic degradation with the applied voltage 4v for 30min. The ·OH that generated in the photo-catalytic degradation process were responsible for Rh-B decomposition. The ·O2- played the significant role in the photo-electro-catalytic degradation of Rh-B. Furthermore, the decarboxylation was also occurred in the photo-electro-catalytic degradation for the Rh-B in water except for the deethylation and hydroxylation in the photo-catalytic degradation. In addition, the toxicities of the intermediates were calculated using the ECOSAR program and the EPIWIN software. The results indicated that the toxicities of intermediates from photo-electro-catalytic degradation for the Rh-B were higher than photo-catalytic degradation, due to the generation of decarboxylate.

Degradation of lincomycin in aqueous solution with hydrothermal treatment: Kinetics, pathway, and toxicity evaluation

Recently, lincomycin has been detected frequently in aquatic environment, especially in the effluent of pharmaceutical wastewater treatment plants. Public concerns have been raised due to its adverse bio-effect and potential of inducing resistance genes. In this study, hydrothermal treatment (HT) was applied to remove lincomycin from high-concentrated pharmaceutical waste water. Influence factors (e.g., temperature, initial concentration and pH) were investigated from kinetics perspective. Meanwhile, degradation byproducts were identified using liquid chromatography–mass spectrometry (LC–MS), based on that transformation pathways were proposed. Finally, the toxicity of lincomycin degradation intermediates were evaluated by Microcystis cells. The results showed that lincomycin was eliminated efficiently via HT and an obvious lag time existed in its degradation process. An autocatalytic model was developed successfully based on the degradation kinetics analysis. The model showed good fitness with experiments data (R2 > 0.99). Observed reaction constant (k) increased when reaction temperature varied from 110 to 160 °C; it decreased from 0.034 to 0.015 min−1 as pH ranged from 2.0 to 6.0. Additionally, increasing initial concentration of lincomycin promoted its degradation, while it showed a different trend once the concentration exceeded 300 mg L−1. A total of 7 major intermediates were identified, based on which hydrolysis, hydroxylation and desulfuration were inferred as the mainly evolution processes. Finally, toxicity evaluation indicated that both lincomycin and its degradation byproducts have no inhibition on algal strains. Thus, it is concluded that HT is an efficient method for removing lincomycin.

A novel electrocatalytic approach for effective degradation of Rh-B in water using carbon nanotubes and agarose.

Carbon nanotubes (CNTs)/agarose (AG) membrane on the ITO (indium tin oxide) conductive glass, with high efficiency of electrocatalytic degradation for rhodamine B (Rh-B) in water, was prepared using an easy and green method. The prepared CNTs/AG membrane was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), energy dispersive spectra (EDS), infrared spectroscopy (IR), and electrochemical impedance spectroscopy (EIS). The results revealed that CNTs were dispersed in the AG membrane. Additionally, the electrocatalytic activities for Rh-B were conducted on the electrochemical workstation with a three-electrode system. Both initial pH and potential played an important role in the process of electrocatalytic degradation. At pH3 and potential reaching 4V, the removal rate of Rh-B (10mg/L) in water achieved 96% within 20min. The stability of the prepared CNTs/AG membrane was also investigated. Besides, the toxicities of the main intermediates from the electrocatalytic degradation for Rh-B were calculated using the ECOSAR program and EPIWIN software, and results indicated that the toxicities of some intermediates were higher than those of the parent pollutant (Rh-B). These findings provided a light-spot to simplify the preparation of efficient working electrode and emphasized the possible potential risks from intermediates at the same time.

Ultrasonic-enhanced Fenton-like degradation of bisphenol A using a bio-synthesized schwertmannite catalyst

Schwertmannite (Sch) was synthesized by Acidithiobacillus ferrooxidans and used as Fenton-like catalyst for bisphenol A (BPA) degradation combining with ultrasonic technology (US). Physicochemical characterizations showed that the bio-synthesized Sch particles had a pompon-like morphology with high BET surface area of 92.92m2/g. The degradation reaction showed a two-stage pseudo-first-order kinetic process consisting of an induction period and a followed rapid degradation period. A synergistic effect existed between US and Sch on activating H2O2 and the synergy factor was calculated to be 2.32. The catalytic efficiency of the system was mainly affected by pH, Sch dosage and temperature, but less relevant to H2O2 concentration. Free OH radicals in the bulk solution were identified to be the dominant oxidant, which were produced by both heterogeneous and homogeneous processes. The promotional effect of US on Fenton-like degradation of BPA can be ascribed to the reasons of (1) increasing the radical generation by ultrasonic cavitation; (2) reducing the apparent activation energies of degradation reaction; (3) accelerating the dissolution of iron and (4) keeping the high surface area of catalyst by continuous surface cleaning. Ecotoxicity tests indicated lower toxicities of intermediates than BPA. In addition, Sch exhibited high reusability in the recycle study.

Efficient activation of peroxymonosulfate by using ferroferric oxide supported on carbon/UV/US system: A new approach into catalytic degradation of bisphenol A

In the present research, a new method of sulfate radical-based advanced oxidation process was developed for the degradation of bisphenol A (BPA). In this regard, magnetite nanoparticles supported on carbon (MNPs@C), as a heterostructure catalyst was combined with UV light and ultrasound (US) irradiation to efficient activate peroxymonosulfate (MNPs@C/UV/US/PMS). Several parameters affecting the degradation efficiency including pH, reaction time, different concentrations of catalyst, BPA and PMS, US power and water matrix components were studied. BPA degradation rate was considerably enhanced when US and UV irradiations were applied simultaneously with MNPs@C for activate PMS. A possible oxidation mechanism and reaction pathway for BPA degradation was proposed. Under optimized conditions, complete removal of BPA was obtained while the mineralization degree was only 56.4%. Toxicity tests with activated sludge demonstrate that MNPs@C/UV/US/PMS system could be improved the biodegradability of the solution. The quenching experiments proved that both OH and SO4− radicals participate significantly during the degradation of BPA and sulfate radicals were dominant species. The MNPs@C also show a high synergistic effect (42.6%) on the BPA degradation in the presence of the other used agents during MNPs@C/UV/US/PMS system. IOUR decreased substantially after 60min treatment, confirming the toxicity of intermediates eliminated by process. The catalytic performance in degrade BPA was decreased at the presence of anions follows the order of HCO3−>H2PO4−>NO3−>SO42−>Cl−. Cycling tests indicate the MNPs@C was reusable to activate PMS for degrade BPA for six consecutive cycles and the removal efficiency still remains at 95.2%. Overall, these results reveal that the activation of PMS by MNPs@C/UV/US system is an efficient and promising advances oxidation technology for the treatment of BPA-contaminated waters and wastewaters.

Synthetic biology for manufacturing chemicals: constraints drive the use of non-conventional microbial platforms.

Genetically modified microbes have had much industrial success producing protein-based products (such as antibodies and enzymes). However, engineering microbial workhorses for biomanufacturing of commodity compounds remains challenging. First, microbes cannot afford burdens with both overexpression of multiple enzymes and metabolite drainage for product synthesis. Second, synthetic circuits and introduced heterologous pathways are not yet as "robust and reliable" as native pathways due to hosts' innate regulations, especially under suboptimal fermentation conditions. Third, engineered enzymes may lack channeling capabilities for cascade-like transport of metabolites to overcome diffusion barriers or to avoid intermediate toxicity in the cytoplasmic environment. Fourth, moving engineered hosts from laboratory to industry is unreliable because genetic mutations and non-genetic cell-to-cell variations impair the large-scale fermentation outcomes. Therefore, synthetic biology strains often have unsatisfactory industrial performance (titer/yield/productivity). To overcome these problems, many different species are being explored for their metabolic strengths that can be leveraged to synthesize specific compounds. Here, we provide examples of non-conventional and genetically amenable species for industrial manufacturing, including the following: Corynebacterium glutamicum for its TCA cycle-derived biosynthesis, Yarrowia lipolytica for its biosynthesis of fatty acids and carotenoids, cyanobacteria for photosynthetic production from its sugar phosphate pathways, and Rhodococcus for its ability to biotransform recalcitrant feedstock. Finally, we discuss emerging technologies (e.g., genome-to-phenome mapping, single cell methods, and knowledge engineering) that may facilitate the development of novel cell factories.

The impact of bladder preparation protocols on post treatment toxicity in radiotherapy for localised prostate cancer patients.

This study compares the post radiotherapy related toxicity between the use of an empty and a full bladder preparation protocol in patients receiving radical radiotherapy for localised prostate cancer. A retrospective review of patient treatment records in which they were treated with a standard radiotherapy schedule (60Gy/20 fractions) to prostates and base of seminal vesicles only and followed two different bladder preparation (empty and full) protocols was carried out. This included each patient's daily image guided radiotherapy (IGRT) setup, treatment time, bladder size on planning computed tomography, organs at risk dose volume histograms (OAR DVHs) and 12 months post treatment gastrointestinal (GI) and genitourinary (GU) toxicity data. 20 patients were included. There were significant differences in IGRT setup between the two groups. Although treatment times of the two groups were not significantly different, 5/200 (2.5%) sessions were longer than 20 min in the full bladder group while this was not found in the other group.Associations between bladder preparation protocols and GI (p = 1.0) and GU (p = 0.6) toxicities were not statistically significant. The bladder size on planning CT was not significantly correlated to the GI (R = 0.06, p = 0.8) or GU (R = 0.27, p = 0.3) toxicity scores. No significant differences were found in OAR DVHs between patients with and without GI and GU toxicities. No grade 3/4 toxicities were reported. The empty bladder preparation approach has non-inferior acute and intermediate post RT GI and GU toxicities in patients treated for localised prostate cancer with advanced radiotherapy techniques compared to the full bladder preparation.

Major Reaction Coordinates Linking Transient Amyloid-β Oligomers to Fibrils Measured at Atomic Level

The structural underpinnings for the higher toxicity of the oligomeric intermediates of amyloidogenic peptides, compared to the mature fibrils, remain unknown at present. The transient nature and heterogeneity of the oligomers make it difficult to follow their structure. Here, using vibrational and solid-state nuclear magnetic resonance spectroscopy, and molecular dynamics simulations, we show that freely aggregating Aβ40 oligomers in physiological solutions have an intramolecular antiparallel configuration that is distinct from the intermolecular parallel β-sheet structure observed in mature fibrils. The intramolecular hydrogen-bonding network flips nearly 90°, and the two β-strands of each monomeric unit move apart, to give rise to the well-known intermolecular in-register parallel β-sheet structure in the mature fibrils. Solid-state nuclear magnetic resonance distance measurements capture the interstrand separation within monomer units during the transition from the oligomer to the fibril form. We further find that the D23–K28 salt-bridge, a major feature of the Aβ40 fibrils and a focal point of mutations linked to early onset Alzheimer’s disease, is not detectable in the small oligomers. Molecular dynamics simulations capture the correlation between changes in the D23–K28 distance and the flipping of the monomer secondary structure between antiparallel and parallel β-sheet architectures. Overall, we propose interstrand separation and salt-bridge formation as key reaction coordinates describing the structural transition of the small Aβ40 oligomers to fibrils.

First clinical report of helical tomotherapy with simultaneous integrated boost for synchronous bilateral breast cancer.

Radiotherapy (RT) for synchronous bilateral breast cancer (SBBC) is technically very challenging. This study reports the clinical feasibility, dosimetry and safety of helical tomotherapy (HT) with simultaneous integrated boost (SIB) in patients treated with adjuvant radiotherapy for SBBC. 21 women with SBBC treated with HT from January 2013 to June 2016 were retrospectively evaluated. Radiation lung toxicity was assessed using pulmonary function test (PFT) and high-resolution computerized tomography scan (HRCT) scan at baseline and 1 yearpost-RT in 18 patients. Survival was calculated using Kaplan-Meier curves. Significance of the difference between pre- and post-RT PFT values was assessed using paired t-test. The dose prescription was 50Gy to the breast, chest wall or regional nodes and 61Gy to the tumour bed as SIB, delivered in 25 fractions. Dosimetric outcome was excellent both for target volumes and normal tissues. Acute skin and oesophageal toxicities were minimal. Symptomatic radiation-induced pnuemonitis was not observed. Subclinical radiological Grade I-II changes were apparent in 14 patients. Only one patient developed Grade III radiological change whereas no change was documented for three patients. PFTs did not show any significant change in any of the measured parameters. At a median follow-up of 25 months, 3-year disease-free survival, overall survival and loco-regional control were 65.6%, 83.3% and 85.7% respectively. Women with SBBC can be safely treated with HT and this is not associated with adverse short- to intermediate term radiation toxicity. Advances in knowledge: This is the first report that establishes the safety of HT for adjuvant RT using SIB technique in SBBC.

In Vivo Synthesis of Polyhydroxylated Compounds from a “Hidden Reservoir” of Toxic Aldehyde Species

AbstractSynthetic enzyme cascades in living cells often lack efficiency owing to the formation of byproducts by endogenous enzymes or toxicity of the cascade intermediates. Highly reactive aldehyde species can trigger a metabolic stress response, and this leads to undesired side reactions and decreased yields. Owing to the metabolic background of Escherichia coli (E. coli), aldehydes may be irreversibly oxidized to carboxylic acids or reduced to the corresponding alcohols. Herein, we applied an approach to equilibrate the aldehyde concentration in vivo. We oxidized primary alcohols to the corresponding aldehydes by AlkJ, an alcohol dehydrogenase from Pseudomonas putida. Introduction of a carboxylic acid reductase from Nocardia iowensis allowed the target compound to be retrieved from the carboxylate sink. Further reduction of the aldehydes to alcohols by endogenous E. coli enzymes completed the equilibration between alcohols, aldehydes, and carboxylic acids. Thus, the aldehyde concentrations remained below nonviable concentrations. We demonstrated the concept on several primary alcohols, which reached the redox equilibrium within 6 h and persisted up to 24 h. Subsequent combination with a dihydroxyacetone‐dependent aldolase (Fsa1‐A129S, E. coli) demonstrated that the reactive aldehyde species were freely available and gave the aldol product, (3S,4R)‐1,3,4‐trihydroxy‐5‐phenylpentan‐2‐one, in 70 % yield within short reaction times.

Oxidation of benzalkonium chloride in aqueous solution by S2O82−/Fe2+ process: Degradation pathway, and toxicity evaluation

The present study is to investigate the treatment of a disinfectants wastewater containing benzalkonium chloride (BAC) by S2O82−/Fe2+ process and microbial fuel cell (MFC) system was applied as bio-sensor for the toxicity test of degradation products. The operating oxidation conditions have been optimized. The optimal condition for the degradation of BAC were: pH=5.0, [S2O82−]/[Fe2+]=1:2, the removal rate of BAC reaches 91.45%, and the COD removal efficiency was 52.46% after 60min. The degradation intermediates were identified by GC–MS and the degradation pathway of BAC was proposed. The toxicity and biodegradability of intermediates of BAC after being treated by S2O82−/Fe2+ oxidation was analyzed by MFC system. The generated power of MFC system was closely related to the initial concentration of BAC. The voltage output and maximal power density were increased from 25.42mV and 1.01mW/m2 to 37.80mV and 12.13mW/m2 after 100mg L−1 BAC was treated by S2O82−/Fe2+ oxidation process. These results indicated that the S2O82−/Fe2+ oxidation shows positive effect for enhancing the biodegradability of intermediates.