Digital Commons Network^™

Methylome–Proteome Integration After Late-Life Voluntary Exercise Training Reveals Regulation And Target Information For Improved Skeletal Muscle Health, Toby L Chambers, Andrea Dimet-Wiley, Alexander R Keeble, Amin Haghani, Wen-Juo Lo, Gyumin Kang, Robert Brooke, Steve Horvath, Christopher S Fry, Stanley J Watowich, Yuan Wen, Kevin A Murach

Physiology Faculty Publications

Abstract: Exercise is a potent stimulus for combatting skeletal muscle ageing. To study the effects of exercise on muscle in a preclinical setting, we developed a combined endurance–resistance training stimulus for mice called progressive weighted wheel running (PoWeR). PoWeR improves molecular, biochemical, cellular and functional characteristics of skeletal muscle and promotes aspects of partial epigenetic reprogramming when performed late in life (22–24 months of age). In this investigation, we leveraged pan-mammalian DNA methylome arrays and tandem mass-spectrometry proteomics in skeletal muscle to provide detailed information on late-life PoWeR adaptations in female mice relative to age-matched sedentary controls (n = 7–10 …

Nonresolving Neuroinflammation Regulates Axon Regeneration In Chronic Spinal Cord Injury, Andrew N. Stewart, Christopher C. Bosse-Joseph, Reena Kumari, William M. Bailey, Kennedy A. Park, Victoria K. Slone, John C. Gensel

Physiology Faculty Publications

Chronic spinal cord injury (SCI) lesions retain increased densities of microglia and macrophages. In acute SCI, macrophages induce growth cone collapse and facilitate axon retraction away from lesion boundaries. Little is known about the role of sustained inflammation in chronic SCI or whether chronic inflammation affects regeneration. We used the colony-stimulating factor-1 receptor inhibitor, PLX-5622, to deplete microglia and macrophages months after complete crush SCI in female mice. Transcriptional analyses revealed a significant inflammatory depletion within chronic SCI lesions after PLX-5622 treatment. Both transcriptional analyses and immunohistochemistry revealed that Iba1⁺ cells repopulate to predepleted densities after treatment removal. Neuronal-enriched …

Programmable Scanning Diffuse Speckle Contrast Imaging Of Cerebral Blood Flow, Faezeh Akbari, Xuhui Liu, Fatemeh Hamedi, Mehrana Mohtasebi, Li Chen, Lei Chen, Guoqiang Yu

Physiology Faculty Publications

Significance: Cerebral blood flow (CBF) imaging is crucial for diagnosing cerebrovascular diseases. However, existing large neuroimaging techniques with high cost, low sampling rate, and poor mobility make them unsuitable for continuous and longitudinal CBF monitoring at the bedside. Aim: We aimed to develop a low-cost, portable, programmable scanning diffuse speckle contrast imaging (PS-DSCI) technology for fast, high-density, and depth-sensitive imaging of CBF in rodents. Approach: The PS-DSCI employed a programmable digital micromirror device (DMD) for remote line-shaped laser (785 nm) scanning on tissue surface and synchronized a 2D camera for capturing boundary diffuse laser speckle contrasts. New algorithms were developed …

Differential Effects Of Myosin Activators On Myocardial Contractile Function In Nonfailing And Failing Human Hearts, Joohee Choi, Patrick T. Wood, Joshua B. Holmes, Katherine L. Dominic, Cristobal G. Dos Remedios, Kenneth S. Campbell, Julian E. Stelzer

Physiology Faculty Publications

The second-generation myosin activator danicamtiv (DN) has shown improved function compared with the first-generation myosin activator omecamtiv mecarbil (OM) in nonfailing myocardium by enhancing cardiac force generation but attenuating slowed relaxation. However, whether the functional improvement with DN compared with OM persists in remodeled failing myocardium remains unknown. Therefore, this study aimed to investigate the differential contractile responses to myosin activators in nonfailing and failing myocardium. Mechanical measurements were performed in detergent-skinned myocardium isolated from donor and failing human hearts. Steady-state force, stretch activation responses and loaded shortening velocity were analyzed at submaximal [Ca2+] in the absence or presence of …

S6k1 Is A Targetable Vulnerability In Tumors Exhibiting Plasticity And Therapy Resistance, Saptadwipa Ganguly, Ravshan Burikhanov, Vitaliy M. Sviripa, Sally Ellingson, Jieyun Jiang, Christian M. Gosser, David Orren, Eva M. Goellner, Gautham G. Shenoy, Mahadev Rao, John D’Orazio, Christine F. Brainson, Chang Guo Zhan, Peter H. Spielmann, David S. Watt, Vivek M. Rangnekar

Physiology Faculty Publications

Background: Most tumors initially respond to treatment, yet refractory clones subsequently develop owing to resistance mechanisms associated with cancer cell plasticity and heterogeneity. Methods: We used a chemical biology approach to identify protein targets in cancer cells exhibiting diverse driver mutations and representing models of tumor lineage plasticity and therapy resistance. An unbiased screen of a drug library was performed against cancer cells followed by synthesis of chemical analogs of the most effective drug. The cancer subtype target range of the leading drug was determined by PRISM analysis of over 900 cancer cell lines at the Broad Institute, MA. RNA-sequencing …

Sex-Based Differences In The Long-Term Fate Of Hippocampal Neurons Born After A Traumatic Brain Injury, Hannah C. Downing, Ashley B. Glover, Jessica E. Gebhardt, Katherine L. Thompson, Kathryn E. Saatman

Physiology Faculty Publications

Introduction: Moderate-to-severe traumatic brain injury (TBI) results in an early loss of immature hippocampal granule cells and the activation of typically quiescent neural stem cells (NSCs) in the dentate gyrus. Activation of NSCs leads to a robust increase in proliferation and generation of neural progenitor cells (NPCs), supporting restoration of the immature neuron population of over a period of 1–2 weeks. However, it is unclear if neurons born early after injury develop normally, survive long-term and functionally integrate into the hippocampal network. Although adult hippocampal neurogenesis is regulated in a sex-dependent manner, the majority of pre-clinical TBI studies lack the …

Skeletal Muscle Stem Cell Mitochondria Are Transferred To Muscle Fibers In Response To A Hypertrophic Stimulus, Jensen Goh, Julia G. Williams, Sarah E. Ogle, Jai K. Joshi, Logan N. Scott, Benjamin Burke, Alex R. Keeble, Nicholas T. Thomas, Christopher S. Fry, Ahmed Ismaeel, John J. Mccarthy

Physiology Faculty Publications

The fusion of skeletal muscle stem cell (MuSC) to myofibers during hypertrophy has exclusively focused on the transfer of the MuSC nucleus, leaving the fate of other MuSC organelles, such as mitochondria, largely unexplored. The objective of this study was to determine whether MuSCs transfer their mitochondria upon myofiber fusion in response to a hypertrophic stimulus. To achieve this goal, we specifically labeled MuSC mitochondria with Dendra2 fluorescence by crossing the MuSC-specific CreER (Pax7^CreER/CreER) mouse with the Rosa26-Dendra2 mouse to generate the Pax7-Dendra2 mouse. To induce the fusion of MuSC to myofibers, Pax7-Dendra2 mice underwent synergist ablation surgery …

Breaking Ground On Self-Efficacy: A Qualitative Exploration Of Intimate Partner Violence Survivors’ Experiences With Therapeutic Horticulture, Rachel Marie Reeves

Theses and Dissertations--Sociology

This dissertation explores how participation in a Therapeutic Horticulture program may support the self-efficacy of survivors of Intimate Partner Violence. Through a thematic analysis of interviews with 45 women living at a domestic violence shelter in Lexington, Kentucky, this study investigates whether and how gardening activities contributed to participants’ belief in their abilities to shape outcomes in their lives.

Findings are organized around Bandura’s four sources of self-efficacy: enactive mastery experiences, vicarious experience, verbal persuasion, and physiological/affective states. These insights contribute to feminist criminology and trauma-informed care literature by illuminating the transformative potential of nature-assisted healing programs.

Investigating Relatedness Within Breeding Units Of The Highly Social Bushtit (Psaltriparus Minimus), Fiona Skye Connelly

Theses and Dissertations--Biology

Cooperative breeding systems represent an array of varied reproductive strategies and remain a topic of interest in behavioral ecology (i.e., Riehl 2013, Cornwallis et al. 2017). Different manifestations of cooperative breeding, such as cooperative polyandry, no doubt have unique evolutionary pressures tied to local ecologies which have led to their proliferation. Of particular interest are species that show flexibility in their use of reproductive strategies, wherein individuals may choose one strategy over another given a specific circumstance. Here, I used double-digest restriction site-associated DNA sequencing (i.e., ddRAD-seq) to investigate bushtit (Psaltriparus minimus) reproductive strategies and the relatedness between …

Temporal Dynamics Of Programmed Genome Rearrangement In Sea Lamprey Embryogenesis: A Deep Learning & Lightsheet Imaging Approach To Studying Early Developmental Transitions, Kasturi Rajandran

Theses and Dissertations--Biology

Programmed genome rearrangement (PGR) in the sea lamprey (Petromyzon marinus) leads to the elimination of ~0.5Gb (20%) of the germline genome during early embryogenesis, yet its timing relative to the maternal-to-zygotic transition (MZT) remains unclear. In this study, we imaged embryos cleared at 3-hour intervals (up to 72 hours post fertilization (hpf)) using high-resolution lightsheet fluorescence microscopy and a custom deep-learning image-analysis pipeline (~80% accuracy) to quantify nuclei and micronuclei counts. Micronuclei, which are the hallmarks of PGR first appear between 24 to 27hpf (vs ~36hpf previously reported) indicating PGR starts earlier than previously reported in the sea …

The Role Of Metabolic Gate Keepers In Cell Fate Decision Making, Brian Kelly

Theses and Dissertations--Biology

Maintaining cellular energy balance and redox stability is crucial to cell survival, with glutamine metabolism playing a central role. While extensively studied in cancer, where it supports biosynthesis and reduces oxidative stress to promote tumor growth, its function in non-cancerous contexts like tissue development and muscle regeneration remains less understood. A key aspect of stem cell biology is quiescence, a metabolically dormant state that preserves the stem cell pool, yet the mechanisms regulating this state are not fully clear. Here, we identify glutamine metabolism as a critical factor governing myoblast proliferation and quiescence through a metabolic program distinct from that …

Engaging Nurses In Effective Cost Of Care Conversations To Address Cancer-Related Financial Toxicity: Results From An Exploratory Survey, Jean Edward, Amanda T. Wiggins, Louis G. Baser, Haafsah Fariduddin, Joanna F. Doran, Monica F. Bryant, John August D'Orazio, Kimberly D. Northrip

Markey Cancer Center Faculty Publications

Few evidence-based trainings exist on how to equip healthcare providers, particularly nurses, with the skills to engage in cost of care conversations with patients/caregivers to mitigate the impact of cancer-related financial toxicity. This study evaluated a pilot training developed in collaboration with Triage Cancer® to prepare oncology nurses to identify and assist patients/caregivers facing financial and/or legal barriers to care. Ten pediatric oncology nurses completed the training and pre/post-surveys on behaviors related to financial and legal need screening, frequency and comfort level of answering questions, knowledge, and behavior changes, along with training evaluation questions. At baseline, six nurses reported never …

Pharmacological Or Genetic Inhibition Of Ltcc Promotes Cardiomyocyte Proliferation Through Inhibition Of Calcineurin Activity, Lynn A. C. Devilée, Abou Bakr M. Salama, Jessica M. Miller, Janice D. Reid, Qinghui Ou, Nourhan M. Baraka, Kamal Abou Farraj, Madiha Jamal, Yibing Nong, Todd K. Rosengart, Douglas A. Andres, Jonathan Satin, Tamer M. A. Mohamed, James E. Hudson, Riham R. E. Abouleisa

Markey Cancer Center Faculty Publications

Cardiomyocytes (CMs) lost during ischemic cardiac injury cannot be replaced due to their limited proliferative capacity. Calcium is an important signal transducer that regulates key cellular processes, but its role in regulating CM proliferation is incompletely understood. Here we show a robust pathway for new calcium signaling-based cardiac regenerative strategies. A drug screen targeting proteins involved in CM calcium cycling in human embryonic stem cell-derived cardiac organoids (hCOs) revealed that only the inhibition of L-Type Calcium Channel (LTCC) induced the CM cell cycle. Furthermore, overexpression of Ras-related associated with Diabetes (RRAD), an endogenous inhibitor of LTCC, induced CM cell cycle …

Urobilin Derived From Bilirubin Bioconversion Binds Albumin And May Interfere With Bilirubin Interacting With Albumin: Implications For Disease Pathology, Kevin I. Williams, Priyanka Suryadevara, Chang-Guo Zhan, Terry D. Hinds Jr., Zachary A. Kipp

Markey Cancer Center Faculty Publications

Background/Objectives: Bilirubin is a hydrophobic molecule that binds the carrier protein albumin for transport through systemic circulation. Bilirubin is cleared from the body through the liver and excreted into the intestines, where the microbiota modifies the chemical structure, forming urobilin, which can be reabsorbed into circulation by the hepatic portal vein. Urobilin has no known function. It is also unknown whether urobilin binds albumin for transport in circulation. We hypothesized that because of the likeness of their chemical structures, urobilin would also bind albumin like bilirubin does. Methods: First, we used in silico docking to predict if urobilin would bind …

Heme Oxygenase, Biliverdin Reductase, And Bilirubin Pathways Regulate Oxidative Stress And Insulin Resistance: A Focus On Diabetes And Therapeutics, Wang-Hsin Lee, Zachary A. Kipp, Sally Pauss, Genesee J. Martinez, Evelyn A. Bates, Olufunto O. Badmus, David E. Stec, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Metabolic and insulin-resistant diseases, such as type 2 diabetes mellitus (T2DM), have become major health issues worldwide. The prevalence of insulin resistance in the general population ranges from 15.5% to 44.6%. Shockingly, the global T2DM population is anticipated to double by 2050 compared with 2021. Prior studies indicate that oxidative stress and inflammation are instrumental in causing insulin resistance and instigating metabolic diseases. Numerous methods and drugs have been designed to combat insulin resistance, including metformin, thiazolidinediones (TZDs), sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP1RA), and dipeptidyl peptidase 4 inhibitors (DPP4i). Bilirubin is an antioxidant with …

Mir-27a-3p Regulates Intestinal Cell Proliferation And Differentiation Through Wnt/Β-Catenin Signalling, Chang Li, Yuning Zhou, Yinping Jiang, Zhijie Yin, Heidi L. Weiss, Qingding Wang, B. Mark Evers

Markey Cancer Center Faculty Publications

Intestinal stem cells differentiate into absorptive enterocytes, characterised by increased brush border enzymes such as intestinal alkaline phosphatase (IAP), making up the majority (95%) of the terminally differentiated cells in the villus. Loss of integrity of the intestinal epithelium plays a key role in inflammatory diseases and gastrointestinal infection. Here, we show that the intestinal microRNA (miR)-27a-3p is an important regulator of intestinal epithelial cell proliferation and enterocyte differentiation. Repression of endogenous miR-27a-3p leads to increased enterocyte differentiation and decreased intestinal epithelial cell proliferation in mouse and human small intestinal organoids. Mechanistically, miR-27a-3p regulates intestinal cell differentiation and proliferation at …

Engaging Nurses In Effective Cost Of Care Conversations To Address Cancer-Related Financial Toxicity: Results From An Exploratory Survey, Jean Edward, Abigail Wiggins, Louis G. Baser, Haafsah Fariduddin, Joanna F. Doran, Monica F. Bryant, John A. D'Orazio, Kimberly D. Northrip

Markey Cancer Center Faculty Publications

Few evidence-based trainings exist on how to equip healthcare providers, particularly nurses, with the skills to engage in cost of care conversations with patients/caregivers to mitigate the impact of cancer-related financial toxicity. This study evaluated a pilot training developed in collaboration with Triage Cancer® to prepare oncology nurses to identify and assist patients/caregivers facing financial and/or legal barriers to care. Ten pediatric oncology nurses completed the training and pre/post-surveys on behaviors related to financial and legal need screening, frequency and comfort level of answering questions, knowledge, and behavior changes, along with training evaluation questions. At baseline, six nurses reported never …

Biparental Inheritance Of Germline-Specific Chromosomes In The Sea Lamprey And Their Roles In Oocytes, Vladimir A. Timoshevskiy, Nataliya Timoshevskaya, Kaan İ. Eşkut, Kasturi Rajandran, Jeramiah J. Smith

Markey Cancer Center Faculty Publications

Many eukaryotic species undergo programmed elimination of specific chromosomes during embryogenesis, typically retaining these chromosomes only in their germ cells. In some species, programmatic elimination of GRCs, or sex chromosomes, also occurs in a sex-specific manner, with specific chromosomes being transmitted or eliminated by only one sex. As such, these chromosomes provide a unique perspective on the evolution of gene functions that are advantageous to the germline and genetic tradeoffs between somatic vs germline or oocyte vs sperm biology. While GRCs have been extensively characterized in male sea lampreys (Petromyzon marinus), the status of GRCs in females has not yet …

Analysis Of Facilitators Of And Barriers To Enactment Of State Regulation Of Indoor Tanning By Minors, Carolyn J. Heckman, Anna Mitarotondo, David B. Buller, Julia Berteletti, Kevin Schroth, Jerod L. Stapleton, Robert P. Dellavalle

Markey Cancer Center Faculty Publications

Background: Indoor tanning (IT) causes skin cancers, including potentially deadly melanoma. IT often starts during youth, a critical time for deleterious skin damage. About half of the US states have enacted laws banning IT for minors under age 18.

Purpose: This study reports qualitative findings from interviews with key informants (KIs) involved in IT legislative efforts to identify/describe factors influencing law enactment, based on the multiple streams framework.

Methods: Guided by expert advisors and using snowball-sampling, KIs from 16 states with most recently enacted IT laws regulating minor access and states without restrictions were contacted. In virtual interviews, KIs shared …

Cisplatin-Loaded M1 Macrophage-Derived Vesicles Have Anti-Cancer Activity In Osteosarcoma, Namrata Anand, Joseph Robert Mccorkle, David Schweer, Lan Li, Kristen S. Hill, Melissa A. Fath, Derek B. Allison, Christopher L. Richards, Jill M. Kolesar

Markey Cancer Center Faculty Publications

Osteosarcoma (OS) is a relatively rare bone malignancy that primarily affects children and young adults and is associated with significant morbidity and mortality. Cisplatin is a mainstay of treatment, but its efficacy is limited by off-target toxicities. Immunotherapy is not effective due to a poor antigenic tumor microenvironment. Here, we address these challenges by using manufactured M1 macrophage-derived vesicles (MVs) loaded with cisplatin. Human blood and mouse RAW 264.7 M1 macrophages were used to prepare empty (E-MVs) and cisplatin-loaded MVs (C-MVs). Human OS cell lines were used in vitro and in a tibia xenograft mouse model to evaluate the anti-cancer …

Characterizing Agroecosystem Effects Of Industrial Hemp On A Rotational Row Cropping System And Microbial Communities, Kent D. Pham

Theses and Dissertations--Plant and Soil Sciences

The implementation of crop rotation on a farm can have many benefits for agroecosystem health and production. This practice can potentially reduce nutrient amendments, disrupt pest and disease cycles, and increase crop yields. In Kentucky, one common rotation consists of either corn or soybean grown the first year, followed by the other crop, repeated every two years. Industrial hemp, grown for fiber or grain, is an emerging crop that has shown promise as a rotation alternative, although not much is known about its effects on soil health, agroecosystem functioning, and microbial communities. To better characterize hemp’s role within American agriculture, …

Factors Impacting Germination, Emergence, And Establishment Of Direct Seeded And Transplanted Hemp (Cannabis Sativa L.), Paul Cockson Dr.

Theses and Dissertations--Plant and Soil Sciences

Industrial hemp (IH) establishment has many challenges including: poor emergence, low stand establishment, and variable plant development in direct seeded hemp. In floral hemp production, quality transplant production is a challenge with seedlings often becoming root bound and etiolated. In both direct seeded and transplant hemp, the relationship between root vigor and vegetative growth has not been studied and may prove insightful for managing emergence and establishment challenges. The goals of this study were three-fold: 1) to measure and describe root system architecture (RSA) and root phenotypes observed in selected IH cultivars especially in regard to identifying agronomically important RSA …

Fault Identification And Localization In Distribution Grids Based On An Attention-Hybrid Graph Neural Network, Xingjian Shan

Theses and Dissertations--Electrical and Computer Engineering

This thesis proposes a multi-task fault diagnosis framework for distribution systems based on Graph Convolutional Networks (GCN) and an enhanced Graph Attention Network (GATv2). By representing the power grid as a graph with electrical features and topological connections, the model simultaneously performs fault type classification and fault location prediction. The architecture incorporates residual connections, multi-head attention, and a Jumping Knowledge module to capture multi-scale structural patterns, while dynamic loss weighting ensures balanced task optimization under noise and sparsity. Experimental results on the IEEE 123-node test feeder demonstrate a fault classification accuracy of 96.43%, and fault localization accuracies of 84.64% (strict), …

Fusarium Head Blight Resistance Genes Impact Agronomic Performance, Flavor, Milling, And Baking Traits In Soft Red Winter Wheat, Joyce Morris

Theses and Dissertations--Plant and Soil Sciences

Fusarium Head Blight (FHB) is an economically devastating disease of wheat (Triticum aestivum L.) causing low yields and poor quality. FHB, caused by Fusarium graminearum, disrupts the grain filling phase and results in bleached spikes and shriveled seeds. Deoxynivalenol (DON) is a mycotoxin produced by the fungal pathogen when it infects the plant; DON is harmful when consumed by humans and causes feed rejection in livestock. Using FHB resistant varieties and timely applications of fungicides is the optimum strategy for management of this disease. However, there has been little research focusing on the impact of FHB resistance genes …

Influence Of Industrial Hemp On Soil Health Parameters In A Kentucky Cropping System, Jack T. Eaker

Theses and Dissertations--Plant and Soil Sciences

Industrial hemp (fiber, floral, and grain: Cannabis sativa L.) legalization has prompted research into its incorporation into agronomic rotations and impacts on agroecosystem services such as nutrient dynamics. This study quantified the effects of integrating grain and fiber hemp on soil health, hypothesizing hemp would positively impact soil health due to its taproot, reported C benefits, and nutrient requirements. Conducted in Kentucky at two locations, a completely randomized block design included six crop rotation treatments, with soil cores collected at initiation (2020) and post three growing seasons (2023). Soil parameters analyzed included particulate organic matter, short-term CO2 mineralization, water-extractable organic …

Giving Props To Soil Property Predictive Models: Utilizing Mir To Predict Soil Health Properties, Diala M. Abboud

Theses and Dissertations--Plant and Soil Sciences

Soil health is critical to sustaining life on Earth, influencing plant growth, agricultural productivity, water quality, and overall ecosystem sustainability. In response to climate change and intensifying land use, the need to improve our understanding of soil health has become increasingly urgent. The application of mid-infrared (MIR) spectroscopy coupled with statistical modeling has emerged as a promising, cost-effective approach to predict soil health parameters, offering a quicker alternative to traditional wet chemistry analyses. MIR methods have been successfully applied to predict various soil health properties, such as bulk density (BD), cation exchange capacity (CEC), base saturation (BS), electrical conductivity (EC), …

Chemoproteomic Profiling Of A Carbon-Stabilized Gold(Iii) Macrocycle Reveals Cellular Engagement With Hmox2, Sailajah Gukathasan, Chibuzor Ngozi Olelewe, Libby Ratliff, Jong H. Kim, Alyson M. Ackerman, J. Robert Mccorkle, Sean Parkin, Gunnar F. Kwakye, Jill M. Kolesar, Samuel G. Awuah

Chemistry Faculty Publications

In this work, we discovered a novel organometallic gold(III) macrocycle, Au-Mac1, that demonstrates anticancer potency in a panel of triple-negative breast cancer cells (TNBC), and based on this complex, a biotinylated-Au-Mac1 probe was designed for target identification via chemoproteomics, which uncovered the engagement of HMOX2 of the heme-energy metabolism pathway. Using orthogonal chemical biology and molecular biology approaches, including immunoblotting, flow cytometry, and cellular thermal shift assays, it was confirmed that Au-Mac1 engages HMOX2 in cells. Downstream effects of Au-Mac1 on the depletion of mitochondrial membrane proteins and bioenergetics point to the potential role of HMOX2 in cancer. Importantly, Au-Mac1 …

Caspase-11 And Nlrp3 Exacerbate Systemic Klebsiella Infection Through Reducing Mitochondrial Ros Production, Yuqi Zhou, Zhuodong Chai, Ankit Pandeya, Ling Yang, Yan Zhang, Guoying Zhang, Congqing Wu, Zhenyu Li, Yinan Wei

Chemistry Faculty Publications

Introduction: Klebsiella pneumoniae is a Gram-negative bacterium and the third most commonly isolated microorganism in blood cultures from septic patients. Despite extensive research, the mechanisms underlying K. pneumoniae-induced sepsis and its pathogenesis remain unclear. Acute respiratory failure is a leading cause of mortality in systemic K. pneumoniae infections, highlighting the need to better understand the host immune response and bacterial clearance mechanisms. Method: To investigate the impact of K. pneumoniae infection on organ function and immune response, we utilized a systemic infection model through intraperitoneal injection in mice. Bacterial loads in key organs were quantified, and lung injury was assessed. …

Bacteria-Engineered Vesicles For Cancer Immunotherapy: From Immunomodulation In Vitro To Anti-Tumor Effects In Melanoma Models, Lan Li

Theses and Dissertations--Chemistry

Bacterial vesicles hold immense potential in various biomedical fields. Among these, outer membrane vesicles (OMVs) produced by Gram-negative bacteria are the most extensively studied. While the exact mechanism of OMV production remains unclear, numerous environmental factors have been shown to influence both their yield and composition. In this study, we investigated the effect of three different antimicrobial families on OMV production by E. coli. Interestingly, antimicrobials within the same family did not provide the same effects on OMV yield, suggesting that OMV production may not directly correlate with the antimicrobial mechanism of action. OMVs have demonstrated tumor-inhibitory activity in multiple …

Catalytic Deoxygenation Of Oleaginous Biomass To Renewable Diesel And Sustainable Aviation Fuel Via Decarboxylation/Decarbonylation, Chukwudalu Great Umenweke

Theses and Dissertations--Chemistry

Several technologies have been developed to produce hydrocarbon biofuels – renewable diesel (RD) and sustainable aviation fuel (SAF) – from fats, oils, and greases (FOG), with the hydroprocessing of esters and fatty acids (HEFA) representing one of the most mature pathways. In its current form, HEFA is mainly reliant on the hydrodeoxygenation (HDO) reaction, which has several drawbacks since HDO requires large amounts and pressures of hydrogen, feedstocks of high purity and cost, as well as problematic sulfided catalysts that risk contaminating the biofuel product with sulfur. A process based on decarboxylation/decarbonylation (deCO_x) offers an attractive alternative to …