Algal Extracellular Organic Matter Induced Photochemical Oxidation of Mn(II) to Solid Mn Oxide: Role of Mn(III)-EOM Complex and Its Ability to Remove 17α-Ethinylestradiol.

Photosensitizer-mediated abiotic oxidation of Mn(II) can yield soluble reactive Mn(III) and solid Mn oxides. In eutrophic water systems, the ubiquitous algal extracellular organic matter (EOM) is a potential photosensitizer and may have a substantial impact on the oxidation of Mn(II). Herein, we focused on investigating the photochemical oxidation process from Mn(II) to solid Mn oxide driven by EOM. The results of irradiation experiments demonstrated that the generation of Mn(III) intermediate was crucial for the successful photo oxidization of Mn(II) to solid Mn oxide mediated by EOM. EOM can serve as both a photosensitizer and a ligand, facilitating the formation of the Mn(III)-EOM complex. The complex exhibited excellent efficiency in removing 17α-ethinylestradiol. Furthermore, the complex underwent decomposition as a result of reactions with reactive intermediates, forming a solid Mn oxide. The presence of nitrate can enhance the photochemical oxidation process, facilitating the conversion of Mn(II) to Mn(III) and then to solid Mn oxide. This study deepens our grasp of Mn(II) geochemical processes in eutrophic water and its impact on organic micropollutant fate.

Occurrence and cycle of dissolved iron mediated by humic acids resulting in continuous natural photodegradation of 17α-ethinylestradiol.

17α-ethinylestradiol (EE2), a synthetic endocrine-disrupting chemical, can degrade in natural waters where humic acids (HA) and dissolved iron (DFe) are present. The iron is mostly bound in Fe(III)-HA complexes, the formation process of Fe(III)-HA complexes and their effect on EE2 degradation were explored in laboratory experiments. The mechanism of ferrihydrite facilitated by HA was explored with results indicating that HA facilitated the dissolution of ferrihydrite and the generation of Fe(III)-HA complexes with the stable chemical bonds such as C-O, CO in neutral, alkaline media with a suitable Fe/C ratio. 1O2, •OH, and 3HA* were all found to be important in the photodegradation of EE2 mediated by Fe(III)-HA complexes. Fe(III)-HA complexes could produce Fe(II) and hydrogen peroxide (H2O2) to create conditions suitable for photo-Fenton reactions at neutral pH. HA helped to maintain higher dissolved iron concentrations and alter the Fe(III)/Fe(II) cycling. The natural EE2 photodegradation pathway elucidated here provides a theoretical foundation for investigating the natural transformation of other trace organic contaminants in aquatic environments.

Evaluating non-targeted analysis methods for chemical characterization of organic contaminants in different matrices to estimate children's exposure.

BACKGROUND: Children are vulnerable to environmental exposure of contaminants due to their small size, lack of judgement skills, as well as their proximity to dust, soil, and other environmental sources. A better understanding about the types of contaminants that children are exposed to or how their bodies retain or process these compounds is needed. OBJECTIVE: In this study, we have implemented and optimized a methodology based on non-targeted analysis (NTA) to characterize chemicals in dust, soil, urine, and in the diet (food and drinking water) of infant populations. METHODS: To evaluate potential toxicological concerns associated with chemical exposure, families with children between 6 months and 6 years of age from underrepresented groups were recruited in the greater Miami area. Samples of soil, indoor dust, food, water, and urine were provided by the caregivers, prepared by different techniques (involving online SPE, ASE, USE, QuEChERs), and analyzed by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Data post-processing was performed using the small molecule structure identification software, Compound Discoverer (CD) 3.3, and identified features were plotted using Kendrick mass defect plot and Van Krevelen diagrams to show unique patterns in different samples and regions of anthropogenic compound classifications. RESULTS: The performance of the NTA workflow was evaluated using quality control standards in terms of accuracy, precision, selectivity, and sensitivity, with an average of 98.2%, 20.3%, 98.4% and 71.1%, respectively. Sample preparation was successfully optimized for soil, dust, water, food, and urine. A total of 30, 78, 103, 20 and 265 annotated features were frequently identified (detection frequency >80%) in the food, dust, soil, water, and urine samples, respectively. Common features detected in each matrix were prioritized and classified, providing insight on children's exposure to organic contaminants of concern and their potential toxicities. IMPACT STATEMENT: Current methods to assess the ingestion of chemicals by children have limitations and are generally restricted by specific classes of targeted organic contaminants of interest. This study offers an innovative approach using non-targeted analysis for the comprehensive screening of organic contaminants that children are exposed to through dust, soil, and diet (drinking water and food).

Algal organic matter and dissolved Mn cooperatively accelerate 17α-ethinylestradiol photodegradation: Role of photogenerated reactive Mn(III).

Algal extracellular organic matter (EOM), a major fraction of the dissolved organic matter found in eutrophic plateau lakes, can act as a photosensitizer to drive the abiotic oxidation of Mn(II). This process has the potential to generate reactive Mn(III) and influence the fate of organic pollutants. In this study, the photodegradation of 17α-ethinylestradiol (EE2) in the presence of Mn(II) and EOM was investigated with emphasis on the photogeneration mechanism of Mn(III). The results indicated that Mn(II) can accelerate EE2 photodegradation in EOM solution owing to the photogeneration of reactive Mn(III), and the enhancement was greater at higher Mn(II) concentrations. The generation of reactive Mn(III) was mainly attributable to the action of superoxide radical generated by photosensitization of EOM. In addition, the photodegradation of EE2 was slower at higher pH, possibly because of the deactivation of Mn(III) under alkaline conditions. Single-electron transfer was an indispensable process in the photodegradation. The differences in fluorophore content, pH, and NO3- concentrations are all important determinants for EE2 photodegradation in natural waters. The information obtained in this research would contribute to the understanding of reactions between Mn(II) and EOM, and provide new insights into the behaviors of reactive Mn(III) in eutrophic water irradiated by sunlight.

Non-targeted analysis for the screening and semi-quantitative estimates of per-and polyfluoroalkyl substances in water samples from South Florida environments.

Per- and polyfluoroalkyl substances (PFAS) are a group of anthropogenic pollutants that are found ubiquitously in surface and drinking water supplies. Due to their persistent nature, bioaccumulative potential, and significant adverse health effects associated with low concentrations, they pose a concern for human and environmental exposure. With the advances in high-resolution mass spectrometry (HRMS) methods, there has been an increasing number of non-targeted analysis (NTA) approaches that allow for a more comprehensive characterization of total PFAS present in environmental samples. In this study, we have developed and compared NTA workflows based on an online solid phase extraction- liquid chromatography high resolution mass spectrometry (online SPE-LC-HRMS) method followed by data processing using Compound Discoverer and FluoroMatch for the screening of PFAS in drinking waters from populated counties in South Florida, as well as in surface waters from Biscayne Bay, Key west, and Everglades canals. Tap water showed the highest number of PFAS features, indicating a poor removal of these chemicals by water treatment or perhaps the breakdown of PFAS precursors. The high number of PFAS features identified only by CD and FluoroMatch emphasizes the complementary aspects of these data processing methods. A Semi-quantitation method for NTA (qNTA) was proposed using a global calibration curve based on existing native standards and internal standards, in which concentration estimates were determined by a regression-based model and internal standard (IS) response factors. NTA play a crucial role in the identification and prioritization of non-traditionally monitored PFAS, needed for the understanding of the toxicological and environmental impact, which are largely underestimated due to the lack of such information for many PFAS.

A novel report on phthalates levels in Biscayne Bay surface waters and drinking water from South Florida.

In this research, we have developed and validated a modified version of the U.S.EPA method 506 using a liquid-liquid extraction method followed by gas-chromatography mass spectrometry analysis to assess the occurrence and spatial and seasonal variation of six phthalates (di(2-ethylhexyl) phthalate-DEHP, dibutyl phthalate-DBP, butyl benzyl phthalate-BBP, diethyl phthalate-DEP, dimethyl phthalate-DMP, and di-n-octyl phthalate-DOP) in surface and tap waters from South Florida, collected during the wet and dry seasons. The most frequently detected phthalate was DEHP, with concentrations up to 1.56 µg/L in surface water. Higher DEHP concentrations were observed in tap water during the wet season, which aligns with the higher temperature during the summer months facilitating leaching from plastic materials. Preliminary ecological and human health risk assessments suggested low hazard risk based on concentrations observed in tap and surface waters, respectively. PAEs could however still constitute a great concern to sensitive marine species, including early stages organisms and coral reefs.

Assessment of per- and polyfluoroalkyl substances in Biscayne Bay surface waters and tap waters from South Florida.

Per- and polyfluoroalkyl substances (PFAS) are persistent anthropogenic pollutants present in many environmental media worldwide due to their extensive uses in many industrial and commercial products combined with their high thermal and chemical stabilities. Its ubiquitous presence in surface and drinking water supply and significant adverse health effects observed in wildlife and humans, associated with its bioaccumulation potential, pose big concerns. In this study, we have developed and validated a semi-automated solid phase extraction (SPE) followed by liquid chromatography-mass spectrometry (LC-MS/MS) for the determination of legacy and emerging short-chain PFAS substitutes in surface and tap water at low parts-per-trillion (ppt) levels in South Florida environments. Surface waters from Biscayne Bay and adjacent canals (n = 15) and tap waters from different counties (Miami-Dade, Broward, and Palm Beach County) (n = 21) were collected between October 2020 (wet season) and February 2021 (dry season). Total PFAS concentrations up to 242 ng L-1 (average of 168 ng L-1) were found in tap water from Grapeland Heights, which is the closest location to the Miami international airport that was sampled. The highest average total PFAS level of 106 ng L-1 was observed in surface water from the Biscayne Canal C-8 for the wet and dry season. In general, average total PFAS was higher in tap water (86.3 ng L-1) than in surface waters (46.3 ng L-1), whereas the most predominant and frequently detected PFAS were PFBA, PFBS, PFPeA, PFHxA, PFHxS, PFOA and PFOS. PFAS levels found could represent a high human health risk, and ecological risk based on PFOS levels above recommended thresholds are also noted. Such knowledge on PFAS occurrence, distribution and sources in South Florida will provide essential information for local and regional regulatory agencies related to water quality, further facilitating the development of guidelines and procedures for PFAS pollution control and reduction in Florida.

Enhancement of Chemokine mRNA Expression by Toll-Like Receptor 2 Stimulation in Human Peripheral Blood Mononuclear Cells of Patients with Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease which is often associated with Staphylococcus aureus (S. aureus) colonization. S. aureus ingredients are potential ligands to activate the Toll-like receptor 2 (TLR2) and drive inflammatory cytokine or chemokine production. However, the role of TLR2-mediated chemokine expression in AD development has not been systematically investigated. In this study, we sought to determine the mode of TLR2-mediated chemokine expression in AD patients. Human peripheral blood mononuclear cells (PBMCs) were isolated from AD patients and healthy controls. Upon incubation with TLR2 ligands Pam3CSK4 and PGN, mRNA expression of chemokines, including CCL1, CCL5, CCL8, CCL13, CCL17, CCL18, CCL22, and CCL27, were determined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The results showed that basal mRNA expression of CCL17 in PBMCs from AD patients was upregulated compared with healthy controls, while those of CCL8 and CCL13 were downregulated. When stimulated with TLR2 ligands, the mRNA expression of CCL5, CCL8, CCL13, CCL18, and CCL22 in PBMCs from AD patients was significantly higher than those from healthy controls. The different basal chemokine mRNA expression profiles indicate the different immune status in patients with AD compared with healthy controls. Excessive chemokine mRNA expression induced by TLR2 activation is associated with the development of AD.

A Multiple-Instance Learning-Based Convolutional Neural Network Model to Detect the IDH1 Mutation in the Histopathology Images of Glioma Tissues.

The IDH1 mutation is the most frequent somatic mutation in gliomas, and it has an important impact on the treatment outcome of gliomas. Clinically, the gold standard methods for the IDH mutation detection are the immunohistochemistry and gene sequencing techniques, whereas using the histopathology images of the glioma tissues for IDH mutation identification has not been reported. In this study, we propose a convolutional neural network (CNN) model that is trained on histopathology images of glioma samples using multiple instance learning (MIL), which links the benefits of the end-to-end classification power of the deep neural network with the MIL by aggregating the scores of the instances to the bag-level score. The attention layer is also implemented to facilitate the performance of the MIL aggregation. The results show that our MIL-based CNN model has achieved good performance in the classification of the IDH1 mutation in the glioma images, with the area under the curve of 0.84. Besides, several image segmentation strategies, CNN architectures, and MIL pooling operators have been implemented and analyzed to investigate the effect of these settings on the model performance. To our knowledge, it is the first study to identify the IDH1 mutation by using the histopathology images of the glioma tissues, providing a novel and insightful method for glioma IDH mutation diagnosis.

Multiple "Omics" data-based biomarker screening for hepatocellular carcinoma diagnosis.

The huge prognostic difference between early and late stage hepatocellular carcinoma (HCC) is a challenging diagnostic problem. Alpha-fetoprotein is the mostly widely used biomarker for HCC used in the clinic, however it's sensitivity and specificity of is not optimal. The development and application of multiple biotechnologies, including next generation sequencing, multiple "omics" data, that include genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics has been used for HCC diagnostic biomarker screening. Effective biomarkers/panels/models have been identified and validated at different clinical levels. A large proportion of these have a good diagnostic performance for HCC, especially for early HCC. In this article, we reviewed the various HCC biomarkers derived from "omics" data and discussed the advantages and disadvantages for diagnosis HCC.

Cancer stem cell associated eight gene-based signature predicts clinical outcomes of colorectal cancer.

Previous studies have suggested that cancer stem cells serve crucial functions in tumorigenesis, metastasis and therapy failure. Stem cell signaling transduction pathways are frequently dysregulated in cancer and associated with tumorigenesis, metastasis and the cell cycle, which are necessary for cancer proliferation. However, cancer stem cell-associated gene signatures have not been established for predicting patient outcomes in colorectal cancer. Using a gene-mining approach, the present study performed mRNA expression profiling in large colorectal cancer cohorts from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, including a TCGA colorectal cancer cohort (n=383) and three independent validation series GSE39582 (n=582), GSE17536 (n=177) and GSE17537 (n=55). The present study identified that an eight-gene signature in cancer stem cell signaling was associated with the overall survival and disease/recurrence-free survival of patients with colorectal. On the basis of this signature, patients in the TCGA training sets were divided into high-risk and low-risk subgroups with a significantly different overall survival rate (hazard ratio, 2.38; P=0.0005). The prognostic value of this signature was confirmed using three independent GEO colorectal cancer sets. Identifying this prognostic stem cell signaling signature may provide an efficient classification tool for clinical prognosis evaluation, and facilitate cancer stem cell-targeted therapy.

Fundamental study of the ultrasonic induced degradation of the popular antihistamine, diphenhydramine (DPH).

Diphenhydramine (DPH) the active ingredient in Benadryl, has been detected in streams, rivers and other surface water sources. As a bioactive compound, DPH impacts human health even at low concentrations. Ultrasonic irradiation at 640 kHz leads to the rapid degradation of DPH in aqueous solution. Radical scavenging experiments and detailed product studies indicate the DPH degradation involves direct pyrolysis and degradation reactions mediated by the hydroxyl radicals produced during cavitation. The degradation can be modeled by pseudo-first order kinetics yielding rate constants k of 0.210, 0.130, 0.082, 0.050, 0.035, 0.023 min-1 at the initial concentrations of 2.8, 5.2, 13.9, 27.0, 61.0, 160.0 µmol L-1, respectively. The degradation process follows the Langmuir-Hinshelwood (heterogeneous) model with a partition coefficient, KL-H = 0.06 µmol·L-1and reactivity constant kr = 1.96 µmol min-1·L-1. A competition kinetic study conducted employing the hydroxyl radical trap, coumarin, illustrates that DPH was degraded primarily by hydroxyl radical mediated processes. Computational studies employing Gaussian 09 basis set provide fundamental insight into the partitioning of the reaction pathways and the degradation mechanisms. The study demonstrates the ultrasonic degradation of DPH is rapid, follows simple kinetic expressions and is accurately modeled using computational methods.

Kinetic, product, and computational studies of the ultrasonic induced degradation of 4-methylcyclohexanemethanol (MCHM).

A massive spill of 4-methylcyclohexanemethanol (MCHM), a semi-volatile organic compound, contaminated the Elk river and forced the recent closure of tap water for nearly 300,000 residents. Typical water treatment methods are not effective for MCHM remediation, however ultrasonic irradiation leads to its rapid pseudo-first order degradation. The degradation processes were effectively modeled employing heterogeneous kinetic models with the reaction surface corresponding to the gas-liquid interface of the cavitation bubble. The Freundlich model which takes into account non-uniform distribution within the reactive zone showed the strongest correlation to the observed degradation kinetic data with R2 > 0.99. Solute-solute clustering behavior is proposed to explain non-uniform distribution of MCHM. The results indicate the degradation occurs predominantly at the gas-liquid interface as a result of hydroxyl radical reactions and pyrolysis with primary reaction products, (4-methylcyclohexenyl) methanol and 4-methylcyclohexanone. Computational methods using density functional B3YPL/6-311G** calculations with Gaussian 09 provided insight of the hydroxyl radical and pyrolytic degradation pathways for the isomeric and conformational forms of MCHM. Our studies demonstrate that heterogeneous kinetic models and computational methods are important tools for the fundamental understanding and effective application of ultrasonically mediated degradation of MCHM which may be extended to a number of semi-volatile compounds.