A copper metal-organic framework-based electrochemical sensor for identification of glutathione in pharmaceutical samples.

The construction of a new electrochemical sensing platform based on a copper metal-organic framework (Cu-MOF) heterostructure is described in this paper. Drop-casting Cu-MOF suspension onto the electrode surface primed the sensor for glutathione detection. The composition and morphology of the Cu-MOF heterostructure were investigated using scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HR-TEM), X-ray diffraction spectroscopy (XRD), Fourier transform infrared spectroscopy (FT-IR), and UV-visible spectroscopy. The Cu-MOF heterostructure can identify glutathione (GSH) with an enhanced sensitivity of 0.0437 µA µM-1 at the detection limit (LOD; 0.1 ± 0.005 µM) and a large dynamic range of 0.1-20 µM. Boosting the conductivity and surface area enhances electron transport and promotes redox processes. The constructed sensors were also adequately selective against interference from other contaminants in a similar potential window. Furthermore, the Cu-MOF heterostructure has outstanding selectivity, long-term stability, and repeatability, and the given sensors have demonstrated their capacity to detect GSH with high accuracy (recovery range = 98.2-100.8%) in pharmaceutical samples.

Photocatalytic CO2 Conversion into Solar Fuels Using Carbon-Based Materials-A Review.

Carbon materials with elusive 0D, 1D, 2D, and 3D nanostructures and high surface area provide certain emerging applications in electrocatalytic and photocatalytic CO2 utilization. Since carbon possesses high electrical conductivity, it expels the photogenerated electrons from the catalytic surface and can tune the photocatalytic activity in the visible-light region. However, the photocatalytic efficiency of pristine carbon is comparatively low due to the high recombination of photogenerated carriers. Thus, supporting carbon materials, such as graphene, CNTs (Carbon nanotubes), g-C3N4, MWCNs (Multiwall carbon nanotubes), conducting polymers, and its other simpler forms like activated carbon, nanofibers, nanosheets, and nanoparticles, are usually combined with other metal and non-metal nanocomposites to increase the CO2 absorption and conversion. In addition, carbon-based materials with transition metals and organometallic complexes are also commonly used as photocatalysts for CO2 reduction. This review focuses on developing efficient carbon-based nanomaterials for the photoconversion of CO2 into solar fuels. It is concluded that MWCNs are one of the most used materials as supporting materials for CO2 reduction. Due to the multi-layered morphology, multiple reflections will occur within the layers, thus enhancing light harvesting. In particular, stacked nanostructured hollow sphere morphologies can also help the metal doping from corroding.

Recent Advances on Electrochemical Sensors for Detection of Contaminants of Emerging Concern (CECs).

Contaminants of Emerging Concern (CECs), a new category of contaminants currently in the limelight, are a major issue of global concern. The pervasive nature of CECs and their harmful effects, such as cancer, reproductive disorders, neurotoxicity, etc., make the situation alarming. The perilous nature of CECs lies in the fact that even very small concentrations of CECs can cause great impacts on living beings. They also have a nature of bioaccumulation. Thus, there is a great need to have efficient sensors for the detection of CECs to ensure a safe living environment. Electrochemical sensors are an efficient platform for CEC detection as they are highly selective, sensitive, stable, reproducible, and prompt, and can detect very low concentrations of the analyte. Major classes of CECs are pharmaceuticals, illicit drugs, personal care products, endocrine disruptors, newly registered pesticides, and disinfection by-products. This review focusses on CECs, including their sources and pathways, health effects caused by them, and electrochemical sensors as reported in the literature under each category for the detection of major CECs.

A Two-Pronged Pulmonary Gene Delivery Strategy: A Surface-Modified Fullerene Nanoparticle and a Hypotonic Vehicle.

Inhaled gene therapy poses a unique potential of curing chronic lung diseases, which are currently managed primarily by symptomatic treatments. However, it has been challenging to achieve therapeutically relevant gene transfer efficacy in the lung due to the presence of numerous biological delivery barriers. Here, we introduce a simple approach that overcomes both extracellular and cellular barriers to enhance gene transfer efficacy in the lung in vivo. We endowed tetra(piperazino)fullerene epoxide (TPFE)-based nanoparticles with non-adhesive surface polyethylene glycol (PEG) coatings, thereby enabling the nanoparticles to cross the airway mucus gel layer and avoid phagocytic uptake by alveolar macrophages. In parallel, we utilized a hypotonic vehicle to facilitate endocytic uptake of the PEGylated nanoparticles by lung parenchymal cells via the osmotically driven regulatory volume decrease (RVD) mechanism. We demonstrate that this two-pronged delivery strategy provides safe, wide-spread and high-level transgene expression in the lungs of both healthy mice and mice with chronic lung diseases characterized by reinforced delivery barriers.

MoS2 coated CoS2 nanocomposites as counter electrodes in Pt-free dye-sensitized solar cells.

Expensive Pt counter electrodes remain an obstacle for the commercialization of dye-sensitized solar cells (DSSCs). Therefore, research focusing on low-cost alternative counter electrode materials has been considered important for their commercialization. Here, the fabrication of dye-sensitized solar cells has been performed utilizing CoS2 and MoS2 coated CoS2 nanocomposite materials as the counter electrode, which are synthesized via a hydrothermal route involving low-cost precursor materials. The experimental results obtained from XRD, XPS, EDX, SEM, TEM, and Raman etc. have confirmed the successful formation of CoS2 and MoS2 coated CoS2 nanocomposites. The electrochemical characterization of these materials is performed, which suggests that the electrocatalytic activity towards the liquid iodine electrolyte of these materials is as good as that of the conventional Pt counter electrodes. So, dye-sensitized solar cell devices are fabricated by interpolating a (cis-bis(isothiocyanato)bis(2,2'-bipyridyl-4,4'-dicarboxylato)ruthenium(ii)) dye-loaded TiO2 photoanode and CoS2, MoS2 coated CoS2 and Pt counter electrodes using iodine/iodide as a liquid electrolyte. The devices fabricated with CoS2 counter electrodes have shown an open circuit voltage of 790 mV, a short circuit current of 11.9 mA cm-2, a fill factor of 0.54, and a power conversion efficiency of 6%. On the other hand, the device based on a Pt counter electrode has shown an open circuit voltage of 773 mV, a short circuit current of 13.4 mA cm-2, a fill factor of 0.54, and a power conversion efficiency of 6.6%. In addition, MoS2 coated with a CoS2 counter electrode has shown the best performance with an open circuit voltage of 763 mV, a short circuit current of 20.1 mA cm-2, a fill factor of 0.42, and a power conversion efficiency of 7.6%.

Photocatalytic properties of hierarchical CuO nanosheets synthesized by a solution phase method.

CuO nanomaterials were synthesized by a simple solution phase method using cetyltrimethylammonium bromide (CTAB) as a surfactant and their photocatalytic property was determined towards the visible-light assisted degradation of Reactive Black-5 dye. A detailed mechanism for the formation of CuO nanostructures has been proposed. The effect of various experimental parameters such as catalyst amount, dye concentration, pH and oxidizing agent on the dye degradation efficiency was studied. About 87% dye was degraded at pH2 in the presence of CuO nanosheets under visible light. The enhanced photocatalytic activity of CuO nanosheets can be ascribed to good crystallinity, grain size, surface morphology and a strong absorption in the visible region. CuO is found to be a promising catalyst for industrial waste water treatment.

The 5th world symposium for lymphedema surgery-Recent updates in lymphedema surgery and setting up of a global knowledge exchange platform.

The successful completion of the 5th World Symposium for Lymphedema Surgery (WSLS) marks another milestone in the development and advancement of the management of lymphedema. We present our experience in organizing such a scientific lymphedema conference as well as a summary of seven variable live surgeries used for treating lymphedema. An update of current knowledge and determination of future direction in the treatment of lymphedema was made possible via WSLS 2016. J. Surg. Oncol. 2017;115:6-12. © 2016 Wiley Periodicals, Inc.

Photocatalytic degradation of tartrazine dye using CuO straw-sheaf-like nanostructures.

Straw-sheaf-like CuO nanostructures were fruitfully synthesized using a chemical precipitation approach for the photocatalytic degradation assessment of tartrazine. Phase identification, composition, and morphological outlook of prepared CuO nanostructures were established by X-ray diffraction and scanning electron microscopy analysis. The photocatalytic performance of the synthesized CuO nanostructures was appraised in the presence of visible light and the possible intermediates formed during the photocatalytic degradation were analyzed by gas chromatography-mass spectrometry. A suitable degradation pathway has also been proposed.

Gold Triangular Nanoprisms and Nanodecahedra: Synthesis and Interaction Studies with Luminol toward Biosensor Applications.

Gold triangular nanoprisms and nanodecahedra (pentagonal bipyramids) were synthesized in the absence and presence of nanoseeds by a simple solvothermal synthesis through the reduction of Auric Chloride (HAuCl4) with poly(vinylpyrrolidone) (PVP) in N,N-dimethylformamide (DMF), respectively. These gold nanoparticles exhibit two plasmon resonance bands. The interaction of these gold nanoparticles with luminol was investigated using UV-vis and fluorescence spectroscopy since hefty number of environmental and biological sensors are based on the combination of luminol and gold nanoparticles. The gold nanoparticles quenches the fluorescence of luminol through a static quenching mechanism, i.e., ground state complex formation, which was confirmed by both absorption spectroscopy as well as time-resolved fluorescence spectroscopy. The Stern-Volmer quenching constant and the effective quenching constant determine that gold nanodecahedra has more interaction with luminol than that of triangular gold nanoprisms. The distance between the gold nanoparticles and luminol, calculated using FRET theory, is less than 8 nm, which indicates efficient energy transfer during interaction. These results are expected to be useful for the development of novel sensors.

The versatility of profunda femoral artery perforator flap for oncological reconstruction after cancer resection-Clinical cases and review of literature.

BACKGROUND: The profunda feomris artery perforator (PAP) flap was recently revisited and gains popularity as an alternative method of autologous breast reconstruction. The purpose of this article is to demonstrate that PAP flap can be used reliably for reconstruction of various soft tissue defects. METHODS: A total of 55 free PAP flaps and 16 pedicle PAP flaps were transferred in 63 patients. Each case was reviewed to verify a PAP flap was performed identifying defect location, flap size, flap design, and postoperative complications. RESULTS: Seven flaps in five patients underwent breast reconstructions, 48 patients underwent head and neck reconstructions using free PAP flaps. The mean perforator number was 1.9, and the average pedicles length was 9.7 cm. The majority of perforators were musculocutaneous, and the others were septocutaneous. The mean ischemia time was 121.4 min. Minor complications included wound poor healing, flap partial necrosis, and pedicle vessels problems. Sixteen pedicle PAP flaps were transferred in 10 patients for vulvar reconstruction. Minor complications included urinary tract infection, poor wound healing, wound infection, hematoma. CONCLUSIONS: The anatomy and number of perforators of PAP flap are reliable with adequate pedicle length. This flap can be an excellent option for reconstruction of most soft tissue defects. J. Surg. Oncol. 2016;114:193-201. © 2016 Wiley Periodicals, Inc.

Synthesis of morphology-controlled bismutite for selective applications.

Bismutite (Bi2O2CO3) possessing diverse morphologies, namely nanosheets, nanodiscs and nanoplatelets, was synthesized by a simple controllable method using bismuth nitrate pentahydrate and urea as precursors in a water/ethylene glycol mixture. The as-synthesized samples showed unique physical and chemical properties, such as varying morphology, phase identification, chemical composition, surface area and surface potential. Bi2O2CO3 nanosheets exhibited excellent adsorption capabilities for anionic dyes (acid orange 7 and methyl orange) and high photocatalytic performance for the decolorization of cationic dyes (rhodamine B and methylene blue) under simulated solar illumination. Furthermore, the electrochemical performance of Bi2O2CO3 nanosheets showed good capacitance properties and hence could be a potential candidate for electrode materials in energy related applications.

Sonochemical Synthesis of Layered Copper Hydroxy Nitrate Nanosheets.

Sonochemical reduction of copper nitrate, using 20 kHz ultrasound in aqueous solutions in the presence of urea, led to the formation of layered copper hydroxy nitrate nanosheets, as evidenced by scanning and transmission electron microscopy images. Fourier-transform infrared, X-ray diffraction, and X-ray photoelectron spectroscopy analyses were used to characterize layered Cu2(OH)3NO3 nanosheets. The ultrasound-assisted progressive hydrolysis of urea and in situ formation of Cu(0) through the sonochemical reduction process induced homogeneous nucleation and crystallization of layered Cu2(OH)3NO3 nanosheets.

Recent developments in heterogeneous catalyzed environmental remediation processes.

This article reports on recent developments in heterogeneous AOP processes such as photocatalysis, Fenton-like process and catalytic ozonation. The principle, mechanism, and influence of experimental conditions on the degradation of pollutants in heterogeneous catalytic ozonation and the photocatalytic process were discussed. Introducing solid catalysts substantially increased the efficiency of the ozonation process by producing hydroxyl radicals in the degradation process. The different types of catalyst, catalyst dosage, solution pH, ozone flow rate, water matrix and catalytic reusability and stability are reported on here. The list of various semiconductor materials used as photocatalysts, their light absorption properties, various light sources and surface properties such as surface area, pore size and pore volume as a factor in the photocatalytic degradation of various pollutants are discussed. The review article also discussed the pollutants degraded using these three processes.

CAR T-cells targeting FGFR4 and CD276 simultaneously show potent antitumor effect against childhood rhabdomyosarcoma.

Chimeric antigen receptor (CAR) T-cells targeting Fibroblast Growth Factor Receptor 4 (FGFR4), a highly expressed surface tyrosine receptor in rhabdomyosarcoma (RMS), are already in the clinical phase of development, but tumour heterogeneity and suboptimal activation might hamper their potency. Here we report an optimization strategy of the co-stimulatory and targeting properties of a FGFR4 CAR. We replace the CD8 hinge and transmembrane domain and the 4-1BB co-stimulatory domain with those of CD28. The resulting CARs display enhanced anti-tumor activity in several RMS xenograft models except for an aggressive tumour cell line, RMS559. By searching for a direct target of the RMS core-regulatory transcription factor MYOD1, we identify another surface protein, CD276, as a potential target. Bicistronic CARs (BiCisCAR) targeting both FGFR4 and CD276, containing two distinct co-stimulatory domains, have superior prolonged persistent and invigorated anti-tumor activities compared to the optimized FGFR4-specific CAR and the other BiCisCAR with the same 4-1BB co-stimulatory domain. Our study thus lays down the proof-of-principle for a CAR T-cell therapy targeting both FGFR4 and CD276 in RMS.

Critical role of IRF-8 in negative regulation of TLR3 expression by Src homology 2 domain-containing protein tyrosine phosphatase-2 activity in human myeloid dendritic cells.

Despite extensive studies that unraveled ligands and signal transduction pathways triggered by TLRs, little is known about the regulation of TLR gene expression. TLR3 plays a crucial role in the recognition of viral pathogens and induction of immune responses by myeloid DCs. IFN regulatory factor (IRF)-8, a member of the IRF family, is a transcriptional regulator that plays essential roles in the development and function of myeloid lineage, affecting different subsets of myeloid DCs. In this study, we show that IRF-8 negatively controls TLR3 gene expression by suppressing IRF-1- and/or polyinosinic-polycytidylic acid-stimulated TLR3 expression in primary human monocyte-derived DCs (MDDCs). MDDCs expressed TLR3 increasingly during their differentiation from monocytes to DCs with a peak at day 5, when TLR3 expression was further enhanced upon stimulation with polyinosinic-polycytidylic acid and then was promptly downregulated. We found that both IRF-1 and IRF-8 bind the human TLR3 promoter during MDDC differentiation in vitro and in vivo but with different kinetic and functional effects. We demonstrate that IRF-8-induced repression of TLR3 is specifically mediated by ligand-activated Src homology 2 domain-containing protein tyrosine phosphatase association. Indeed, Src homology 2 domain-containing protein tyrosine phosphatase-dephosphorylated IRF-8 bound to the human TLR3 promoter competing with IRF-1 and quashing its activity by recruitment of histone deacetylase 3. Our findings identify IRF-8 as a key player in the control of intracellular viral dsRNA-induced responses and highlight a new mechanism for negative regulation of TLR3 expression that can be exploited to block excessive TLR activation.

Synthesis and electrochemical properties of biporous alpha-Fe2O3 superstructures.

Biporous microsphere, flower and concaved cuboctahedrans like alpha-Fe2O3 superstructures have been synthesized by using a new synthetic method. Hydrothermal reaction of ferric chloride with potassium thiocyanate at 200 degrees C yields self-assembled microsphere, flower, and concaved cuboctahedrans like intermediates in ethanol, water:ethanol (1:1) mixed solvent and in water, respectively. These intermediates were further converted into corresponding alpha-Fe2O3 in a thermal decomposition process at 600 degrees C under oxygen atmospheric conditions. The influence of solvent, hydrothermal temperature, and concentration of iron precursors on the intermediate morphology was studied, and the growth mechanism has also been proposed. The synthesized intermediates and alpha-Fe2O3 were characterized using X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), high resolution transmission electron microscopy (HR-TEM) and nitrogen adsorption analysis. The FE-SEM results indicated formation of biporous flowerlike morphology. The electrochemical properties of the flowerlike alpha-Fe2O3 electrodes in a Li-ion battery have been investigated. Plausible formation mechanisms of these intermediates were proposed.

A comparative analysis of carer-employees in Canada over time: a cross-sectional analysis of Canada's General Social Survey, 2012 and 2018.

OBJECTIVES: The aims of the study are to identify trends in the socio-demographic, health, and work profiles of Canadian carer-employees (CEs) over time, as well as the gender difference in the intensity of caring. METHODS: Cross-sectional data from cycles 26 and 32, collected in 2012 and 2018 respectively, of the Canadian General Social Survey (GSS) were used. Logistic, multinomial logistic, and linear regressions were used to estimate how caregiving is associated with caregivers' health, well-being, and work in both cycles. Regressions from both cycles were then compared with chi-square tests for significant differences over time. RESULTS: The proportion of male CEs grew between 2012 and 2018, and women were no longer more likely to be a CE. The intensity of care for female CEs was significantly increased from 2012 to 2018 as compared with their male counterparts. General health (2018: OR = 0.25[0.11, 0.61] vs. 2012: OR = 0.33[0.15, 0.72]) and life satisfaction ([Formula: see text] = -0.42[0.54, -0.30] vs. [Formula: see text] = -0.22[-0.30, -0.14]) were significantly worsened with respect to the role of CEs from 2012 to 2018. CONCLUSION: Our study provides the evidence that CEs' health and well-being have worsened over time, especially for female CEs, indicating that the needs of CEs are growing at a faster rate than the supports available. The results are meaningful in informing and justifying the provision of CE supports at work in order to sustain CEs in the workplace, such as the carer-friendly workplace policies.

RéSUMé: OBJECTIFS: Notre étude vise à cerner les tendances du profil sociodémographique, sanitaire et professionnel des employés soignants (ES) canadiens au fil du temps, ainsi que les différences entre les sexes dans l'intensité des soins. MéTHODE: Nous avons utilisé les données transversales des cycles 26 et 32, collectées en 2012 et en 2018 respectivement, de l'Enquête sociale générale (ESG) du Canada. Nous avons fait appel à la régression logistique, à la régression logistique multinomiale et à la régression linéaire pour estimer les associations entre la prestation de soins et la santé, le bien-être et le travail des soignants lors des deux cycles. Nous avons ensuite comparé les régressions des deux cycles avec les analyses du khi-carré pour cerner les écarts significatifs dans le temps. RéSULTATS: La proportion d'ES de sexe masculin a augmenté entre 2012 et 2018, et les femmes n'affichaient plus une probabilité accrue d'être des ES. L'intensité des soins chez les ES de sexe féminin a augmenté de façon significative entre 2012 et 2018 comparativement à leurs homologues masculins. La santé générale (2018 : RC = 0,25[0,11, 0,61] vs 2012 : RC = 0,33[0,15, 0,72]) et la satisfaction à l'égard de la vie ([Formula: see text] = -0,42[0,54, -0,30] vs [Formula: see text] = -0,22[-0,30, -0,14]) se sont significativement dégradées en ce qui a trait au rôle des ES entre 2012 et 2018. CONCLUSION: Notre étude prouve que la santé et le bien-être des ES se sont dégradées au fil du temps, surtout chez les femmes, ce qui montre que les besoins des ES augmentent plus rapidement que le soutien disponible. Ces résultats contribueront à éclairer et à justifier la prestation de mesures d'aide aux ES afin de les appuyer dans leurs milieux de travail, comme par exemple des politiques conçues pour les soignants en milieu de travail.

Impacts of the COVID-19 pandemic on carer-employees' well-being: a twelve-country comparison.

The aim of this analysis is to assess the potential ways that the COVID-19 pandemic has impacted Canadian carer-employees (CEs) and identify the needs CEs feel is required for them to continue providing care. We assess the similarities and differences in the stresses CEs faced during COVID-19 globally across countries in the G7, Australia, Spain, Brazil, Taiwan, India, and China. We aim to compare Canada against global trends with respect to the challenges of the COVID-19 pandemic, as well as the supports in place for CEs. The study utilized 2020 Carer Well-Being Index at the country level. Descriptive data on Canadian CEs is first reviewed, followed by comparisons, by country, on responses relating to: (a) time spent caring; (b) sources of support; (c) impact on paid work and career, and; (d) emotional/mental, financial, and physical health. The relationship between government support and emotional/mental health is also explored. When compared to pre-pandemic times, CEs in Canada on average spent more time caregiving, with 34% reporting more difficulty balancing their paid job and caring responsibilities. Seventy-one percent of CEs feel their mental health has deteriorated. Thirty-four percent of Canadian CEs received support from the government, and only 30% received support from their employers. Globally, there was a similar trend, with CEs experiencing deteriorating mental health, work impacts, and unmet needs during the pandemic. Comparing the well-being of Canadian CEs with other countries provides an opportunity to evaluate areas where Canadian policies and programs have been effective, as well as areas needing improvement.

Detection of Environmentally Harmful Malathion Pesticides Using a Bimetallic Oxide of CuO Nanoparticles Dispersed over a 3D ZnO Nanoflower.

Super-sensitive malathion detection was achieved using a nonenzymatic electrochemical sensor based on a CuO/ZnO-modified glassy carbon electrode (GCE). Due to the high affinity between the Cu element and the sulfur groups in malathion, the developed CuO-ZnO/GCE sensor may bond malathion with ease, inhibiting the redox signal of the Cu element when malathion is present. In addition to significantly increasing the ability of electron transfer, the addition of 3D-flower-like ZnO enhances active sites of the sensor interface for the high affinity of malathion, giving the CuO-ZnO/GCE composite an exceptional level of sensitivity and selectivity. This enzyme-free CuO-ZnO/GCE malathion sensor demonstrates outstanding stability and excellent detection performance under optimal operating conditions with a wide linear range of malathion from 0 to 200 nM and a low detection limit of 1.367 nM. A promising alternative technique for organophosphorus pesticide (OP) determination is offered by the analytical performance of the proposed sensor, and this method can be quickly and sensitively applied to samples that have been contaminated with these pesticides.

Evaluating the release and metabolism of ricinine from castor cake fertilizer in soils using a LC-QTOF/MS coupled with SIRIUS workflow.

Castor cake is a major by-product generated after castor oil extraction and has been widely used as an organic fertilizer. Once applied to soil, a toxic alkaloid ricinine in castor cake may be released into soils and subsequently taken up by crops, which poses a potential threat to food safety and human health. However, the environmental fate of castor cake derived ricinine in agroecosystems remains unclear. In this study, the release and metabolism of ricinine in soils were conducted using soil pot experiments with different castor cake application rates. The analytical methodology of ricinine quantification in soil pore water was first established using solid phase extraction (SPE) coupled with liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). A non-target screening workflow associated with LC-QTOF/MS and SIRIUS platform was further developed to identify ricinine metabolites in soil pore water. After castor cake application, the ricinine concentrations in soil pore water significantly increased to 297-7990 µg L-1 at 1 day and then gradually decreased to 62.1-3460 µg L-1 at 7 days and 1.70-279 µg L-1 at 14 days for the selected two tested soils with castor cake application rates of 2, 10, and 20 g castor cake/kg soil. In addition, two ricinine metabolites R-194 and R-180 were tentatively identified and one ricinine metabolite N-demethyl-ricinin was confirmed through authentic reference standard for the first time by the developed non-target screening workflow. This study highlights the release and metabolism of toxic alkaloid ricinine in soils once applied castor cake as an organic fertilizer. Ricinine could be released into soil pore water in a short-term after castor cake application and then undergo demethylation, hydroxylation, and hydroxylation followed by methylation metabolisms over time in agroecosystems.