Medicine and Health Sciences Commons^™

Enhanced Degradation Of Methyl Orange And Trichloroethylene With Pnipam-Pmma-Fe/Pd-Functionalized Hollow Fiber Membranes, Rollie Mills, Cameron Tvrdik, Andrew Lin, Dibakar Bhattacharyya

UK CARES Faculty Publications

Trichloroethylene (TCE) is a prominent groundwater pollutant due to its stability, widespread contamination, and negative health effects upon human exposure; thus, an immense need exists for enhanced environmental remediation techniques. Temperature-responsive domains and catalyst incorporation in membrane domains bring significant advantages for toxic organic decontamination. In this study, hollow fiber membranes (HFMs) were functionalized with stimuli-responsive poly-N-isopropylacrylamide (PNIPAm), poly-methyl methacrylate (PMMA), and catalytic zero- valent iron/palladium (Fe/Pd) for heightened reductive degradation of such pollutants, utilizing methyl orange (MO) as a model compound. By utilizing PNIPAm’s transition from hydrophilic to hydrophobic expression above the LCST of 32 ◦C, increased pollutant diffusion …

Making Home: The Role Of Social Networks On Identity, Health, And Quality Of Life Among Rural Lesbian And Gay Older Adults, Marc A. Guest, Elizabeth G. Hunter, Nancy E. Schoenberg

UK CARES Faculty Publications

Background and Objectives: Gay and lesbian older persons face a host of health inequalities related to their identity as they age. Challenges to health access and appropriate social support may be even more exacerbated for those living in rural environments; this may be due to the lack of supportive and affirming social connections. This project aimed to explore and describe the social networks and the relationship of these social networks to identity, health, and quality of life of gay and lesbian individuals in rural communities.

Research Design and Methods: Social network data on network type, size, and social capital were …

Effects Of The Applied Potential On The Performance Of Polysulfone Membranes Functionalized With Sulfonated Polyether Ether Ketone Polymers, Abelline Katusiime Fionah, Kate Mclarney, Aviana Judd, Isabel C. Escobar

UK CARES Faculty Publications

The global water crisis growth has led to a tremendous increase in membrane technology research. Membranes are favored over many other technologies for water treatment because, in principle, they require no chemical additives and can be used isothermally at low temperatures. Membranes that can reject contaminants and salts, produce adequate permeate flux values, and require minimal cleaning are highly demanded. However, most synthesized membranes on the market have associated problems, such as membrane fouling; inverse relationships between flux and solute rejection; and the high cost of synthesis, operation, and maintenance. Therefore, there is a continuied need to produce membranes with …

Long-Term Monitoring Of Clodronate In Equine Hair Using Liquid Chromatography-Tandem Mass Spectrometry, Heather K. Knych, D. S. Mckemie, S. Yim, S. D. Stanley, R. M. Arthur

UK CARES Faculty Publications

Given the potential for long-term inhibition of bone remodeling/healing and detrimental effects to horses in training, bisphosphonates are tightly regulated in horseracing. Hair has proven to be an effective matrix for detection of drug administration to horses and has been particularly effective in detecting drugs for a long period of time post administration. Thus, hair may prove to be a useful matrix for detection of administration of this class of drugs. The objective of the current study was to develop an assay and assess the usefulness of hair as a matrix for long-term detection of clodronate to horses. Seven horses …

Maternal Occupational Exposure To Selected Organic And Chlorinated Solvents And Delivery Of Small-For-Gestational Age Or Preterm Infants, Kristen W. Van Buren, Carissa M. Rocheleau, I‐Chen Chen, Tania A. Desrosiers, Wayne T. Sanderson, Maria D. Politis, Elizabeth C. Ailes, The National Birth Defects Prevention Study

UK CARES Faculty Publications

Background: Potential reproductive effects of organic solvent exposure during pregnancy remain unclear. We investigated the association between maternal occupational exposure during pregnancy to six chlorinated solvents, three aromatic solvents, and Stoddard solvent, and delivery of preterm infants or those born small‐ for‐gestational age (SGA).

Methods: In this case–control study of SGA and preterm birth (PTB) nested within the National Birth Defects Prevention Study (NBDPS) from 1997 to 2011, we analyzed data from 7504 singleton live births without major birth defects and their mothers. Self‐reported information on jobs held in the periconceptional period was assessed for solvent exposure. Unconditional logistic regression …

Engineering Ligand Reactivity Enables High-Temperature Operation Of Stable Perovskite Solar Cells, So Min Park, Mingyang Wei, Jian Xu, Harindi R. Atapattu, Felix T. Eickemeyer, Kasra Darabi, Luke Grater, Yi Yang, Cheng Liu, Sam Teale, Bin Chen, Hao Chen, Tonghui Wang, Lewei Zeng, Aidan Maxwell, Zaiwei Wang, Keerthan Raghavendra Rao, Zhuoyun Cai, Shaik M. Zakeeruddin, Jonathan T. Pham, Chad Risko, Aram Amassian, Mercouri G. Kanatzidis, Kenneth R. Graham, Michael Grätzel, Edward H. Sargent

UK CARES Faculty Publications

Perovskite solar cells (PSCs) consisting of interfacial two- and three-dimensional heterostructures that incorporate ammonium ligand intercalation have enabled rapid progress toward the goal of uniting performance with stability. However, as the field continues to seek ever-higher durability, additional tools that avoid progressive ligand intercalation are needed to minimize degradation at high temperatures. We used ammonium ligands that are nonreactive with the bulk of perovskites and investigated a library that varies ligand molecular structure systematically. We found that fluorinated aniliniums offer interfacial passivation and simultaneously minimize reactivity with perovskites. Using this approach, we report a certified quasi–steady-state power-conversion efficiency of 24.09% …

Ketohexokinase-C Regulates Global Protein Acetylation To Decrease Carnitine Palmitoyltransferase 1a-Mediated Fatty Acid Oxidation, Robert N. Helsley, Se-Hyung Park, Hemendra J. Vekaria, Patrick G. Sullivan, Lindsey R. Conroy, Ramon Sun, María Del Mar Romero, Laura Herrero, Joanna Bons, Christina D. King, Jacob Rose, Jesse G. Meyer, Birgit Schilling, C. Ronald Kahn, Samir Softic

Saha Cardiovascular Research Center Faculty Publications

Background & Aims: The consumption of sugar and a high-fat diet (HFD) promotes the development of obesity and metabolic dysfunction. Despite their well-known synergy, the mechanisms by which sugar worsens the outcomes associated with a HFD are largely elusive. Methods: Six-week-old, male, C57Bl/6 J mice were fed either chow or a HFD and were provided with regular, fructose- or glucose-sweetened water. Moreover, cultured AML12 hepatocytes were engineered to overexpress ketohexokinase-C (KHK–C) using a lentivirus vector, while CRISPR-Cas9 was used to knockdown CPT1a. The cell culture experiments were complemented with in vivo studies using mice with hepatic overexpression of KHK–C and …

A Comparative Effectiveness Study On Opioid Use Disorder Prediction Using Artificial Intelligence And Existing Risk Models, Sajjad Fouladvand, Jeffery Talbert, Linda Phyliss Dwoskin, Heather M. Bush, Amy L. Meadows, Lars E. Peterson, Yash R. Mishra, Steven K. Roggenkamp, Fei Wang, Ramakanth Kavuluru, Jin Chen

Markey Cancer Center Faculty Publications

Opioid use disorder (OUD) is a leading cause of death in the United States placing a tremendous burden on patients, their families, and health care systems. Artificial intelligence (AI) can be harnessed with available healthcare data to produce automated OUD prediction tools. In this retrospective study, we developed AI based models for OUD prediction and showed that AI can predict OUD more effectively than existing clinical tools including the unweighted opioid risk tool (ORT). Data include 474,208 patients’ data over 10 years; 269,748 were females with an average age of 56.78 years. Cases are prescription opioid users with at least …

Emt Activates Exocytotic Rabs To Coordinate Invasion And Immunosuppression In Lung Cancer, Guan-Yu Xiao, Xiaochao Tan, Bertha L. Rodriguez, Don L. Gibbons, Shike Wang, Chao Wu, Xin Liu, Jiang Yu, Mayra E. Vasquez, Hai T. Tran, Jun Xu, William K. Russell, Cara Haymaker, Younghee Lee, Jianjun Zhang, Luisa Solis, Ignacio I. Wistuba, Jonathan M. Kurie

Markey Cancer Center Faculty Publications

Epithelial-to- mesenchymal transition (EMT) underlies immunosuppression, drug resistance, and metastasis in epithelial malignancies. However, the way in which EMT orchestrates disparate biological processes remains unclear. Here, we identify an EMT- activated vesicular trafficking network that coordinates promigratory focal adhesion dynamics with an immunosuppressive secretory program in lung adenocarcinoma (LUAD). The EMT-activating transcription factor ZEB1 drives exocytotic vesicular trafficking by relieving Rab6A, Rab8A, and guanine nucleotide exchange factors from miR-148a-dependent silencing, thereby facilitating MMP14-dependent focal adhesion turnover in LUAD cells and autotaxin-mediated CD8+ T cell exhaustion, indicating that cell- intrinsic and extrinsic processes are linked through a microRNA that coordinates vesicular …

Enhanced Bypass Of Pd-L1 Translation Reduces The Therapeutic Response To Mtor Kinase Inhibitors, Yanan Cao, Qing Ye, Murong Ma, Qing-Bai She

Markey Cancer Center Faculty Publications

Increased PD-L1 expression in cancer cells is known to enhance immunosuppression, but the mechanism underlying PD-L1 upregulation is incompletely characterized. We show that PD-L1 expression is upregulated through internal ribosomal entry site (IRES)-mediated translation upon mTORC1 inhibition. We identify an IRES element in the PD-L1 50-UTR that permits cap-independent translation and promotes continuous production of PD-L1 protein despite effective inhibition of mTORC1. eIF4A is found to be a key PD-L1 IRES-binding protein that enhances PD-L1 IRES activity and protein production in tumor cells treated with mTOR kinase inhibitors (mTORkis). Notably, treatment with mTORkis in vivo elevates PD-L1 levels and reduces …

Integrative Analysis Of Mendelian Randomization And Gene Expression Profiles Reveals A Null Causal Relationship Between Adiponectin And Diabetic Retinopathy, Ao Zhang, Hui Wu, Chi Wang, Suyan Tian

Markey Cancer Center Faculty Publications

Observational studies have been conducted to investigate the correlation between adiponectin and diabetic retinopathy (DR), but no consistent relationship has been established. In this study, we employed an integrative analysis that combined Mendelian randomization (MR) and bioinformatics analyses to comprehensively explore the association between DR and adiponectin, aiming to provide a unified answer of their relationship. Using the inverse-variance weighted (IVW) method, the odd ratio (OR) of developing DR per 1 mg/dL increment in genetically predicted log- transformed adiponectin concentration was estimated to be 0.949 (P = 0.557). Other robust MR methods produced consistent results, confirming the absence of a …

Lung And Colorectal Cancer Disparities In Appalachian Kentucky: Spatial Analysis On The Influence Of Education And Literacy, Nicole Robertson Mph, Todd Burus, Lauren Hudson, Pamela C. Hull, Lee Park, Nathan L. Vanderford

Markey Cancer Center Faculty Publications

Low educational attainment and high cancer incidence and mortality rates have long been a challenge in Appalachian Kentucky. Prior studies have reported disparities in cancer incidence and mortality between Appalachian and non-Appalachian populations, but the influence of education on this disparity has not been extensively studied. Herein, all cancers and two cancer sites with available screenings (colorectal and lung) were joined with education indicators (educational attainment and literacy) and one geographic indicator across all 120 Kentucky counties. This dataset was used to build choropleth maps and perform simple linear and spatial regression to assess statistical significance and to measure the …

Messes: Software For Transforming Messy Research Datasets Into Clean Submissions To Metabolomics Workbench For Public Sharing, P. Travis Thompson, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

In recent years, the FAIR guiding principles and the broader concept of open science has grown in importance in academic research, especially as funding entities have aggressively promoted public sharing of research products. Key to public research sharing is deposition of datasets into online data repositories, but it can be a chore to transform messy unstructured data into the forms required by these repositories. To help generate Metabolomics Workbench depositions, we have developed the MESSES (Metadata from Experimental SpreadSheets Extraction System) software package, implemented in the Python 3 programming language and supported on Linux, Windows, and Mac operating systems. MESSES …

Nac1 Confines Virus‐Specific Memory Formation Of Cd4+ T Cells Through The Rock1‐Mediated Pathway, Liqing Wang, Hao-Yun Peng, Jugal Kishore Das, Anil Kumar, Yijie Ren, Darby J. Ballard, Xiaofang Xiong, Wen Yang, Xingcong Ren, Paul De Figueiredo, Jin-Ming Yang, Jianxun Song

Markey Cancer Center Faculty Publications

Nucleus accumbens‐associated protein 1 (NAC1), a transcriptional cofactor, has been found to play important roles in regulating regulatory T cells, CD8 + T cells, and antitumor immunity, but little is known about its effects on T‐cell memory. In this study, we found that NAC1 expression restricts memory formation of CD4 + T cells during viral infection. Analysis of CD4 + T cells from wild‐type (WT) and NAC1‐ deficient (−/−) mice showed that NAC1 is essential for T‐cell metabolism, including glycolysis and oxidative phosphorylation, and supports CD4 + T‐cell survival in vitro. We further demonstrated that a deficiency of NAC1 downregulates …

The Metabolomics Workbench File Status Website: A Metadata Repository Promoting Fair Principles Of Metabolomics Data, Christian D. Powell, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

Background: An updated version of the mwtab Python package for programmatic access to the Metabolomics Workbench (MetabolomicsWB) data repository was released at the beginning of 2021. Along with updating the package to match the changes to MetabolomicsWB’s ‘mwTab’ file format specification and enhancing the package’s functionality, the included validation facilities were used to detect and catalog file inconsistencies and errors across all publicly available datasets in MetabolomicsWB.

Results: The MetabolomicsWB File Status website was developed to provide continuous validation of MetabolomicsWB data files and a useful interface to all found inconsistencies and errors. This list of detectable issues/errors include format …

Heart Failure Knowledge, Symptom Perception, And Symptom Management In Patients With Heart Failure, Jia-Rong Wu, Chin-Yen Lin, Muna Hassan Hammash, Debra K. Moser

UK CARES Faculty Publications

Background: Prevention of heart failure (HF) exacerbations requires that patients carefully self-manage their condition. Symptom perception is a key component in self-care for patients with HF that involves monitoring for HF symptoms and recognizing symptom changes. Heart failure knowledge is a prerequisite for better symptom perception and symptom management. However, the relationships among HF knowledge, symptom perception, and symptom management remain unclear.

Objective: The aim of this study was to explore the inter-relationships among HF knowledge, symptom monitoring, symptom recognition, and symptom response in patients with HF.

Method: We included 185 patients with HF in this study. Heart failure knowledge …

Health Professionals’ Breastfeeding Practices And Associated Factors: A Cross-Sectional Study, Maria Estela Diniz Machado, Marialda Moreira Christoffel, Luis Guillermo Coca Velarde, Ana Maria Linares, Ana Luiza Dorneles Da Silveira, Ana Leticia Monteiro Gomes, Luciana Rodrigues Da Silva

UK CARES Faculty Publications

Objective: To analyze primary care health professionals’ breastfeeding practices and associated factors.

Method: A cross-sectional and analytical study was carried out with all health professionals working in breastfeeding support in five primary healthcare units, through a self-administered questionnaire. The chi-square test was used with a significance level of 5% to analyze the association of categorical variables with professional practice.

Results: Thirty-eight professionals participated. There was a statistically significant association (p=0.04597) between the variable update on breastfeeding in the last five years and the practice of implementing breastfeeding through support groups. Clinical management, guidance on maternal rights, and support for resolving …

Discovery Of A Potent Highly Biased Mor Partial Agonist Among Diastereomeric C9-Hydroxyalkyl-5-Phenylmorphans., Joshua A. Lutz, Agnieszka Sulima, Eugene S. Gutman, Eric W. Bow, Dan Luo, Sophia Kaska, Thomas E. Prisinzano, Carol A. Paronis, Jack Bergman, Gregory H. Imler, Andrew T. Kerr, Arthur E. Jacobson, Kenner C. Rice

Pharmaceutical Sciences Faculty Publications

All possible diastereomeric C9-hydroxymethyl-, hydroxyethyl-, and hydroxypropyl-substituted 5-phenylmorphans were synthesized to explore the three-dimensional space around the C9 substituent in our search for potent MOR partial agonists. These compounds were designed to lessen the lipophilicity observed with their C9-alkenyl substituted relatives. Many of the 12 diastereomers that were obtained were found to have nanomolar or subnanomolar potency in the forskolin-induced cAMP accumulation assay. Almost all these potent compounds were fully efficacious, and three of those chosen for in vivo evaluation, 15, 21, and 36, were all extremely G-protein biased; none of the three compounds recruited beta-arrestin2. Only one of the …

County Incidence And Geospatial Trends Of Early-Onset Hypertensive Disorders Of Pregnancy In Kentucky, 2008-2017, Courtney J. Walker, Anna Kucharska-Newton, Steven R. Browning, W. Jay Christian

UK CARES Faculty Publications

Background Early‑onset hypertensive disorders of pregnancy (eHDP) are associated with more severe maternal and infant outcomes than later‑onset disease. However, little has been done to evaluate population‑level trends. Therefore, in this paper, we seek to address this understudied area by describing the geospatial and temporal patterns of county‑level incidence of eHDP and assessing county‑level demographics that may be associated with an increased incidence of eHDP.

Methods Employing Kentucky certificates of live and stillbirth from 2008–2017, this ecological study detected county‑level clusters of early‑onset hypertensive disorders of pregnancy using SaTScan, calculated average annual percent change (AAPC) with a join point analysis, …

Hydrogen-Bonding Trends In A Bithiophene With 3- And/Or 4-Pyridyl Substituents, Alison M. Costello, Rebekah Duke, Stephanie Sorensen, Nadeesha Kothalawala, Moses Ogbaje, Nandini Sarkar, Doo Young Kim, Chad Risko, Sean Parkin, Aron J. Huckaba

UK CARES Faculty Publications

To improve the charge-carrier transport capabilities of thin-film organic materials, the intermolecular electronic couplings in the material should be maximized. Decreasing intermolecular distance while maintaining proper orbital overlap in highly conjugated aromatic molecules has so far been a successful way to increase electronic coupling. We attempted to decrease the intermolecular distance in this study by synthesizing cocrystals of simple benzoic acid coformers and dipyridyl-2,2′- bithiophene molecules to understand how the coformer identity and pyridine N atom placement affected solid-state properties. We found that with the 5-(3-pyridyl)-5′-(4-pyridyl)-isomer, the 4- pyridyl ring interacted with electrophiles and protons more strongly. Synthesized cocrystal powders …

Development Of A Definition Of Postacute Sequelae Of Sars-Cov-2 Infection, Tanayott Thaweethai, Sarah E. Jolley, Elizabeth W. Karlson, Emily B. Levitan, Bruce Levy, Grace A. Mccomsey, Lisa Mccorkell, Girish N. Nadkarni, Sairam Parthasarathy, Upinder Singh, Tiffany A. Walker, Caitlin A. Selvaggi, Daniel J. Shinnick, Carolin C. M. Schulte, Rachel Atchley-Challenner, Recover Consortium Authors, Leora I. Horwitz, Andrea S. Foulkes

Saha Cardiovascular Research Center Faculty Publications

IMPORTANCE SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals.

OBJECTIVE To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections.

DESIGN, SETTING, AND PARTICIPANTS Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, …

Diabetes Prevalence And Monitoring In Nonmetropolitan And Metropolitan Areas Within A Commercially Insured U.S. Population, Lindsey R. Hammerslag, Jeffery Talbert

Rural & Underserved Health Research Center Publications

Overview of Key Findings

• Enrollees living in nonmetropolitan areas had 22% higher likelihood of having diabetes, even after controlling for factors like age and region.
• The prevalence of diabetes in 2019-2020 was 7.9% in nonmetropolitan areas and 6.2% in metropolitan areas.
• Annual hemoglobin A1c (HbA1c) testing occurred for 85.1% of nonmetropolitan and 85.7% of metropolitan enrollees with diabetes. After controlling for other factors, we found significantly lower testing for those in nonmetropolitan areas.
• For diabetic enrollees, having an HbA1c test in 2019 was associated with an 8% decrease in the likelihood of non-cardiovascular complications related to diabetes and a 6% …

Maternal Polychlorinated Biphenyl 126 (Pcb 126) Exposure Modulates Offspring Gut Microbiota Irrespective Of Diet And Exercise, Manisha Agarwal, Jessie Hoffman, Sara Y. Ngo Tenlep, Sara Santarossa, Kevin J. Pearson, Alexandra R. Sitarik, Andrea E. Cassidy-Bushrow, Michael C. Petriello

Markey Cancer Center Faculty Publications

The gut microbiota plays an important role throughout the lifespan in maintaining host health, and several factors can modulate microbiota composition including diet, exercise, and environmental exposures. Maternal microbiota is transferred to offspring during early life; thus, environmental exposures before gestation may also modulate offspring microbiota. Here we aimed to investigate the effects of maternal exposure to dioxin-like polychlorinated biphenyls (PCBs) on the microbiota of aged offspring and to determine if lifestyle factors, including maternal exercise or offspring high-fat feeding alter these associations. To test this, dams were exposed to PCB 126 (0.5 μmole/kg body weight) or vehicle oil by …

A Case For Accelerating Standards To Achieve The Fair Principles Of Environmental Health Research Experimental Data, Rance Nault, Matthew C. Cave, Gabriele Ludewig, Hunter N. B. Moseley, Kelly G. Pennell, Tim Zacharewski

Markey Cancer Center Faculty Publications

BACKGROUND: Funding agencies, publishers, and other stakeholders are pushing environmental health science investigators to improve data sharing; to promote the findable, accessible, interoperable, and reusable (FAIR) principles; and to increase the rigor and reproducibility of the data collected. Accomplishing these goals will require significant cultural shifts surrounding data management and strategies to develop robust and reliable resources that bridge the technical challenges and gaps in expertise.

OBJECTIVE : In this commentary, we examine the current state of managing data and metadata—referred to collectively as (meta)data—in the experimental environmental health sciences. We introduce new tools and resources based on in vivo …

A Proposed Fair Approach For Disseminating Geospatial Information System Maps, P. Travis Thompson, Sweta Ojha, Christian D. Powell, Kelly G. Pennell, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

We present a draft Minimum Information about Geospatial Information System (MIaGIS) standard for facilitating public deposition of geospatial information system (GIS) datasets that follows the FaIR (Findable, accessible, Interoperable and Reusable) principles. the draft MIaGIS standard includes a deposition directory structure and a minimum javascript object notation (JSON) metadata formatted file that is designed to capture critical metadata describing GIS layers and maps as well as their sources of data and methods of generation. the associated miagis Python package facilitates the creation of this MIAGIS metadata file and directly supports metadata extraction from both Esri JSON and GEOJSON GIS data …

Creation Of Egd-Derived Gastric Cancer Organoids To Predict Treatment Responses, Hannah Mcdonald, Megan Harper, Kristen S. Hill, Anqi Gao, Angelica L. Solomon, Charles J. Bailey, Miranda Lin, Mautin Barry-Hundeyin, Michael Cavnar, Samuel H. Mardini, Prakash Pandalai, Reema A. Patel, Jill M. Kolesar, Justin A. Rueckert, Lawrence Hookey, Mark Ropeleski, Shaila J. Merchant, Joseph Kim, Mei Gao

Markey Cancer Center Faculty Publications

Gastric adenocarcinoma (GAd) is the third leading cause of cancer-related deaths worldwide. Most patients require perioperative chemotherapy, yet methods to accurately predict responses to therapy are lacking. Thus, patients may be unnecessarily exposed to considerable toxicities. Here, we present a novel methodology using patient-derived organoids (PDOs) that rapidly and accurately predicts the chemotherapy efficacy for GAd patients.

Methods: Endoscopic GAd biopsies were obtained from 19 patients, shipped overnight, and PDOs were developed within 24 h. Drug sensitivity testing was performed on PDO single-cells with current standard-of-care systemic GAd regimens and cell viability was measured. Whole exome sequencing was used to …

Differential Inhibition Of Anaplerotic Pyruvate Carboxylation And Glutaminolysis-Fueled Anabolism Underlies Distinct Toxicity Of Selenium Agents In Human Lung Cancer, Teresa W-M Fan, Jason Winnike, Ahmad Al-Attar, Alex C. Belshoff, Pawel Lorkiewicz, Jin Lian Tan, Min Wu, Richard M. Higashi, Andrew N. Lane

Markey Cancer Center Faculty Publications

Past chemopreventive human trials on dietary selenium supplements produced controversial outcomes. They largely employed selenomethionine (SeM)-based diets. SeM was less toxic than selenite or methylseleninic acid (MSeA) to lung cancer cells. We thus investigated the toxic action of these Se agents in two non-small cell lung cancer (NSCLC) cell lines and ex vivo organotypic cultures (OTC) of NSCLC patient lung tissues. Stable isotope-resolved metabolomics (SIRM) using 13C6-glucose and 13C5,15N2-glutamine tracers with gene knockdowns were employed to examine metabolic dysregulations associated with cell type- and treatment-dependent phenotypic changes. Inhibition of key anaplerotic processes, pyruvate carboxylation (PyC) and glutaminolysis were elicited by …

Green Solvent Mediated Extraction Of Micro- And Nano-Plastic Particles From Water, Jameson R. Hunter, Qi Qiao, Yuxuan Zhang, Qing Shao, Czarena L. Crofcheck, Jian Shi

Markey Cancer Center Faculty Publications

The production of plastic and the amount of waste plastic that enters the ecosystem increases every year. Synthetic plastics gradually break down into particles on the micro‑ and nano‑scale in the environment. The micro‑ and nano‑plastics pose a significant ecological threat by transporting toxic chemicals and causing inflammation and cellular damage when ingested; however, removal of those particles from water is challenging using conventional separation methods. Deep eutectic solvents (DES), a new class of solvents composed of hydrogen bond donors and acceptors, have been proposed as a cheaper alternative to ionic liquids. Hydrophobic DES derived from natural compounds (NADES) show …

Identifying And Sharing Per-And Polyfluoroalkyl Substances Hot-Spot Areas And Exposures In Drinking Water, Sweta Ojha, P. Travis Thompson, Christian D. Powell, Hunter N. B. Moseley, Kelly G. Pennell

Markey Cancer Center Faculty Publications

Exposure to per- and polyfluoroalkyl substances (PFAS) in drinking water is widely recognized as a public health concern. Decision-makers who are responsible for managing PFAS drinking water risks lack the tools to acquire the information they need. In response to this need, we provide a detailed description of a Kentucky dataset that allows decision-makers to visualize potential hot-spot areas and evaluate drinking water systems that may be susceptible to PFAS contamination. The dataset includes information extracted from publicly available sources to create five different maps in ArcGIS Online and highlights potential sources of PFAS contamination in the environment in relation …

Noncovalent Interactions That Tune The Reactivities Of The Flavins In Bifurcating Electron Transferring Flavoprotein, María González-Viegas, Rajiv K. Kar, Anne-Frances Miller, Maria-Andrea Mroginski

Markey Cancer Center Faculty Publications

Bifurcating electron transferring flavoproteins (Bf-ETFs) tune chemically identical flavins to two contrasting roles. To understand how, we used hybrid quantum mechanical molecular mechanical calculations to characterize noncovalent interactions applied to each flavin by the protein. Our computations replicated the differences between the reactivities of the flavins: the electron transferring flavin ( ETflavin) was calculated to stabilize anionic semiquinone (ASQ) as needed to execute its single-electron transfers, whereas the Bf flavin (Bfflavin) was found to disfavor the ASQ state more than does free flavin and to be less susceptible to reduction. The stability of ETflavin ASQ was attributed in part to …