Discovery of (meth)acrylate polymers that resist colonization by fungi associated with pathogenesis and biodeterioration

© 2020 The Authors. Fungi have major, negative socioeconomic impacts, but control with bioactive agents is increasingly restricted, while resistance is growing. Here, we describe an alternative fungal control strategy via materials operating passively (i.e., no killing effect). We screened hundreds of (meth)acrylate polymers in high throughput, identifying several that reduce attachment of the human pathogen Candida albicans, the crop pathogen Botrytis cinerea, and other fungi. Specific polymer functional groups were associated with weak attachment. Low fungal colonization materials were not toxic, supporting their passive, anti-attachment utility. We developed a candidate monomer formulation for inkjet-based 3D printing. Printed voice prosthesis components showed up to 100% reduction in C. albicans biofilm versus commercial materials. Furthermore, spray-coated leaf surfaces resisted fungal infection, with no plant toxicity. This is the first high-throughput study of polymer chemistries resisting fungal attachment. These materials are ready for incorporation in products to counteract fungal deterioration of goods, food security, and health

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Studies of Photochemistry in Some Indoor and Outdoor Environments

The impacts of photochemistry can be observed in our everyday lives. This thesis explores two small portions of this daily importance, by highlighting its impact on tracking our oceans’ primary productivity, and the air we breathe inside our homes. Chlorophyll fluorescence can be correlated to phytoplankton in our oceans. We look at chlorophyll, to examine the fluorescence quenching rate constants of common seawater components such as halides (Cl-,Br-,I-) and Iron(III). We do this by comparing spectra which show fluorescence intensity of pure chlorophyll in comparison to this same solution’s fluorescence in the presence of sea water quenchers. In a second study, we show that paints specifically marketed to be photoactive can produce NOx compounds such as (NO,NO2,HONO) from the aqueous deposition of nitrate (NO3-) and gas (NO) phase at 0 and 50 % RH, under illumination sources found indoors (fluorescent ,xenon, incandescent). These gaseous species can be important sources of indoor ozone and OH, which impact the oxidation capacity indoorsM.Sc

Photochemical Production of Carbon Monoxide from Dissolved Organic Matter: Role of Lignin Methoxyarene Functional Groups

Carbon monoxide (CO) is the second most abundant identified product of dissolved organic matter (DOM) photodegradation after CO2, but its formation mechanism remains unknown. Previous work showed that aqueous photodegradation of methoxy-substituted aromatics (ArOCH3) produces CO considerably more efficiently than aromatic carbonyls. Following on this precedent, we propose that the methoxy aromatic groups of lignin act as the C source for the photochemical formation of CO from terrestrial DOM via a two-step pathway: formal hydrolytic demethylation to methanol and methanol oxidation to CO. To test the reasonableness of this mechanism, we investigated the photo-chemistry of eight lignin model compounds. We first observed that initial CO production rates are positively correlated with initial substrate degradation rates only for models containing at least one ArOCH3 group, regardless of other structural features. We then confirmed that all ArOCH3-containing substrates undergo formal hydrolytic demethylation by detecting methanol and the corresponding phenolic transformation products. Finally, we showed that hydroxyl radicals, likely oxidants to initiate methanol oxidation to CO, form during irradiation of all models. This work proposes an explicit mechanism linking ubiquitous, abundant, and easily quantifiable DOM functionalities to CO photoproduction. Our results further hint that methanol may be an abundant (yet overlooked) DOM photoproduct and a likely precursor of formaldehyde, formic acid, and CO2 and that lignin photodegradation may represent a source of hydroxyl radicals

Photochemical renoxification on commercial indoor photoactive paint

Abstract Surface chemistry plays an important role in the indoor environment owing to the large indoor surface to volume ratio. This study explores the photoreactivity of surfaces painted with a photoactive paint in the presence of NOx. Two types of experiments are performed; illumination of painted surfaces with a nitrate deposit and illumination of painted surfaces in the presence of gaseous NO. For both types of experiments, illumination with a fluorescent bulb causes the greatest change in measured gaseous NOx concentrations. Results show that relative humidity and paint composition play an important role in the photoreactivity of indoor painted surfaces. Painted surfaces could contribute to gas-phase oxidant concentrations indoors

Photochemical Production of Carbon Monoxide from Dissolved Organic Matter: Role of Lignin Methoxyarene Functional Groups

Carbon monoxide (CO) is the second most abundant identified product of dissolved organic matter (DOM) photodegradation after CO2, but its formation mechanism remains unknown. Previous work showed that aqueous photodegradation of methoxy-substituted aromatics (ArOCH3) produces CO considerably more efficiently than aromatic carbonyls. Following on this precedent, we propose that the methoxy aromatic groups of lignin act as the C source for the photochemical formation of CO from terrestrial DOM via a two-step pathway: formal hydrolytic demethylation to methanol and methanol oxidation to CO. To test the reasonableness of this mechanism, we investigated the photochemistry of eight lignin model compounds. We first observed that initial CO production rates are positively correlated with initial substrate degradation rates only for models containing at least one ArOCH3 group, regardless of other structural features. We then confirmed that all ArOCH3-containing substrates undergo formal hydrolytic demethylation by detecting methanol and the corresponding phenolic transformation products. Finally, we showed that hydroxyl radicals, likely oxidants to initiate methanol oxidation to CO, form during irradiation of all models. This work proposes an explicit mechanism linking ubiquitous, abundant, and easily quantifiable DOM functionalities to CO photoproduction. Our results further hint that methanol may be an abundant (yet overlooked) DOM photoproduct and a likely precursor of formaldehyde, formic acid, and CO2 and that lignin photodegradation may represent a source of hydroxyl radicals.ISSN:0013-936XISSN:1520-585

Visible light photocatalytic water remediation strategies using a novel black TiO2 based material optimized for in-flow applications

Contaminated drinking water is a major health hazard in large urban areas as well as remote communities. Several pollutants detected in untreated wastewater are hormonal disruptors which are harmful to consumers as well as aquatic life. In this contribution, we present a novel material designed for visible light driven decontamination of water. This material is based on a glass fiber support loaded with black TiO2, a modified form of TiO2 with an expanded light absorption capacity without any toxic metal or non-metal dopants. The photocatalyst developed in our laboratories is ideal for flow as the active material remians fixed while there is continous passage of solution occuring under visible light irradiation. The effectiveness of the catalyst is demonstrated with crocin and 17β-estradiol, the former being a natural carotenoid used as a screening tool, and the latter being a common hormonal disruptor. Our work shows that under visible light illumination, our supported black TiO2 is able to degrade these water contaminants with greater efficiency than conventional TiO2. Using this framework we envision that our findings can contribute to the production of inexpensive, large-scale solar or LED-based water decontamination systems which would be rapidly deployable to sites in need. Operation of such systems would require minimal training and could be monitored remotely. In addition to the catalyst’s non-toxicity and in-flow compatibility, the material also has a long shelf life and is easy and inexpensive to produce, making it an attractive candidate for developing water treatment device

Photocatalytic Hydrogen Generation Using Metal-Decorated TiO₂: Sacrificial Donors vs True Water Splitting

Photocatalytic Hydrogen Generation Using Metal-Decorated TiO₂: Sacrificial Donors vs True Water Splittin