Toxicology Commons^™

Elucidation Of Micro/Nanoplastic Signature Of Human And Murine Lung Tissue Utilizing Pyrolysis-Gas Chromatography/Mass Spectrometry, Aerlin D. Decker

Pharmaceutical Sciences ETDs

Micro-and Nanoplastics (MNPs) are ubiquitous biological pollutants that have been identified throughout a variety of biological samples. MNPs have been detected in several human tissues, such as the brain, kidneys, and liver. Lung tissue remains understudied for MNP accumulation despite the large surface area and clear path for exposure. Using Pyrolysis-Gas Chromatography Mass Spectrometry (Py-GC/MS), human lung tissue was evaluated for 12 different polymers, enabling quantification of total plastic per gram of tissue to be identified. Further analysis was performed with Inductively Coupled Plasma Mass Spectrometry (ICP-MS) to investigate heavy metal accumulation in human lung samples and determine whether a …

Fish Tissue Digestion And Microplastic Polymer Identification Protocol Using Open-Source Ftir Database, Shawn L. Kissinger, Vick-Ariel Privert, Jason Bystriansky, Kyle A. Grice

DePaul Discoveries

Microplastic (MP) contamination in aquatic ecosystems poses significant concerns for environmental and public health, as seafood represents a critical food source worldwide. Despite increasing evidence of MP presence in marine organisms, efficient and accessible detection methods remain essential for characterizing contamination patterns and informing regulatory frameworks. This study extracted MPs from brain, gill, intestine, liver, and muscle tissues of gilt-head bream (Sparus aurata) and European sea bass (Dicentrarchus labrax), two commercially important species from the Gulf of Cádiz, Spain, using a NaOH–HNO₃ chemical digestion protocol. Isolated particles were characterized by Fourier Transform Infrared (FTIR) spectroscopy, with …

Environmental Mercury Alters Immune Pathways Linked To Autoimmune Risk In Mice Mirroring Humans, Maurgan Lee, Paul Stemmer, Randall Gill, Allen Rosenspire, Anil Aranha, Heather Gibson

Medical Student Research Symposium

Background and Purpose: Mercury is a pervasive environmental contaminant, and human epidemiologic studies have linked chronic low-level exposure to increased autoimmune disease-risk. Dysregulated lymphocyte activation and impaired signaling tolerance are central mechanisms in human autoimmunity. Protein phosphorylation governs lymphocyte differentiation and function, alterations in phosphoproteomic networks may represent a signature of immune disruption. This study evaluates how low dose mercury exposure modifies B and T cell abundance and intracellular signaling patterns in BALB/c and Diversity Outbred (DO) mice.

Methods: BALB/c and DO mice were exposed to low dose HgCl2 in their water for two weeks or provided standard water controls. …

The Legacy Of Lead: Lead Exposure's Harmful Effects And Its Concentration In Poc Communities, Layla Sophronia Barber

Student Theses 2015-Present

This thesis examines the disproportionate burden of lead exposure carried by low income, POC communities. The systemic nature of this problem is a symptom of a longstanding legacy of environmental injustice in the United States. Decades of federal neglect are reflected in the higher statistics of lead exposure and poisoning in predominantly black communities. While it is understood that lead exposure poses a serious threat to physical health and early cognitive development, there is a discouraging lack of urgency to remove the toxin from non-wealthy communities. The material covered by this thesis aims to identify and correct the discriminatory social …

False Halos: A Case Of Digoxin Poisoning, Usman Nazeer, Sarita Thanedar, Jacob Sanderson, Gongkai Liu, Hitesh Gidwani

Central & West Texas and San Antonio GME Research Day 2026

No abstract provided.

Effects Of Tubulin-Binding Medications On Microplastic Uptake And Cyotoskeletal Functionality Across Diverse Cell Types, Alejandra D. Favela Santos

Posters - 2026

• Microtubules are composed of of a- and b- tubulin heterodimers, vital for cell structure, shape, and intracellular transport • Microtubules are also useful as they separate chromosomes during cell division • Microplastics (< 5 mm) are considered a health threat and have been found throughout the whole body (1) o In several studies, microplastics have been correlated to higher rates cardiorespiratory issues, endocrine disruption, and cancer (1) • Tubulin-binding medications are widely used as chemotherapeutic agents as they are known for disrupting cell division and targeting tubulin (2,3) o In this study, these medications were used to determine whether microtubules play a role in microplastic uptake § Colchicine typically binds to tubulins and arrests polymerization and growth § Nocodazole disrupts polymerization and prevents spindle formation § Vinblastine inhibits microtubule assembly and disruptions miotic spindle formation.

• The purpose of this study was to determine if different concentrations of tubulin-binding medications affect microplastic uptake o C2C12, RAW 264.7, and MOVAS cell lines were used to evaluate whether these changes are cell type specific 

If microtubule dynamics are disrupted, microplastic uptake can be affect in a concentration-dependent and cell type- specific manner.

The Timing Of Pubertal Onset Affects Adults Anxiety Behavior In A Sex-Specific Manner, Evan Raubenolt

Honors Projects

This study aims to look at the relationship between the timing of pubertal onset and its long-term effects on adult anxiety behavior in rats. Though the topic of pubertal onset has been frequently discussed in developmental research, its exact effects have been inconsistent. Human models have shown that early and late maturing males are associated with a notable increase in adult anxiety behavior, while in rat models, similar sex-specific effects regarding anxiety have been demonstrated, though those studies focus on a causal relationship between exposure to stress and age of pubertal onset. This study first aims to examine that relationship …

Unsaturated Fatty Acid Oil-Based Microdroplets: A Promising Novel Class Of Microdroplets, Ramiz S. Alejilat

Seton Hall University Dissertations and Theses (ETDs)

Droplet-based microfluidics has rapidly advanced numerous fields, including chemistry, biology, materials science, medicine, food science, and cosmetics. In these systems, fluorocarbon oil combined with fluorinated surfactants is the preferred medium for fluid encapsulation, offering exceptional stability and biocompatibility essential for sensitive biological and chemical processes. However, growing concerns about the environmental and biological risks associated with fluorinated chemicals have prompted a search for alternatives.

This study is the first to explore the use of unsaturated fatty acids derived from emu oil for microdroplet formation. We characterized droplet formation based on flow rates and the presence non-fluorinated surfactant at a certain …

Menthalactone From Mentha Piperita L., A Monocot-Selective Bioherbicide, Adam Soltani

Honors Theses

The challenge of managing invasive weed species continues to affect the agricultural industry, presenting ecological, economic, and agronomic hurdles that lead to over 100 billion USD in annual crop losses globally. One such concern is the management of Agrostis stolonifera L., commonly known as creeping bentgrass, particularly due to its ability to form hybrids. This scenario underscores the urgent need for innovative, effective, and environmentally sustainable herbicides, steering the focus toward natural substances as potential candidates. We report here a promising natural lactone, commonly known as menthalactone, which is derived from Mentha piperita L. Its phytotoxic activity was assessed against …

Rising Use Of Immune Checkpoint Inhibitors And The Escalating Burden Of Gastrointestinal And Hepatic Toxicities: A Nine-Year Analysis, Donghyun Ko, Do Han Kim Md, Pedro Palacios Argueta Md, Wilhelm S. Basegoda Md, Jose A. Porres, Francis F. Fadi, Jana G. Hashash, Francis A. Farraye, Paul T. Kroner Md

Posters

The advent of immune checkpoint inhibitors (ICIs), including programmed death 1 (PD-1), PD-L1, and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, has revolutionized cancer therapeutics, markedly improving survival in various malignancies. However, their expanding utilization has been paralleled by the emergence of immune-related adverse events (irAEs), particularly gastrointestinal (GI) and hepatic toxicities, which pose significant challenges in clinical practice. These toxicities can manifest as a spectrum of conditions, from mild transient symptoms to severe, life-threatening complications, necessitating a better understanding of their prevalence and trends. This study aims to evaluate the temporal changes in ICI use and associated GI and hepatic …

Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley

Theses and Dissertations

Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …

Passive Electronic Cigarette Exposure Initiates Squamous Metaplasia In A Developing 3d Human Tracheobronchial Epithelial Tissue In-Vitro Model, Edgar Rolon

Electronic Theses, Projects, and Dissertations

The prevalence of vaping has rapidly increased. ECs are often perceived as less harmful than tobacco cigarettes. A recent meta-analysis showed electronic cigarette (EC) aerosols adversely affected the respiratory system, similar to cigarette smoke, with some effects specific to EC use. Failure to prevent these alterations could lead to life-long comorbidities, and predisposition to respiratory diseases, including COPD and squamous cell carcinoma. While these effects are the result of active vaping, EC aerosols can also settle on indoor surfaces, be absorbed passively through the skin or orally, enter the blood stream, and subsequently expose internal organs, including the airway basal …

Assessing The Behavioral Impact Of Pyridostigmine Bromide In Rats, Noah A. Martin

Honors Theses

Pyridostigmine bromide (PB) is an organophosphate (OP) nerve agent prophylactic used to protect warfighters against chemical warfare agents. OPs inhibit the neural enzyme acetylcholinesterase (AChE) in the brain. This leads to the buildup of acetylcholine, causing respiratory failure, seizures, and death. PB functions by inhibiting ~30% of peripheral AChE temporarily, protecting the enzymes so that the body is able to restore sufficient cholinergic function post-exposure. PB does not cross the blood-brain barrier, though it may still indirectly affect toxicity in the brain due to repeated AChE inhibition throughout treatment, or by inhibition of non-target ChE’s in the blood. The aim …

Zonal Hepatocellular Responses To Acute Ethanol: Impacts On Mitochondrial Function And Metabolism, Matthew T. Savoca

MUSC Theses and Dissertations

Background: Ethanol (EtOH) consumption causes hepatocellular mitochondrial depolarization (mtDepo) and mitophagy. Here, the Aims were to develop techniques to characterize sublobular hepatocellular metabolism and the distribution of mtDepo and mitophagy after acute EtOH. Methods: Wildtype and GFP-LC3 transgenic mice were treated with EtOH or vehicle and administered the covalently labeling mitochondrial membrane potential (ΔΨ) reporter, MitoTracker Red (MTR), and/or the non-covalent ΔΨ reporter, rhodamine 123 (Rh123), prior to intravital imaging, liver fixation, or hepatocyte isolation. After in vivo MTR, hepatocytes were isolated and sorted. Enrichment in E-cadherin (ECAD) and cytochrome P4502E1 in periportal (PP) and pericentral (PC) hepatocytes, respectively, validated …

Investigating Mercury Contamination In Urban Fish: Atomic Absorption Spectroscopy And Histological Analysis For Environmental And Human Health, Indy L. Cockrill, Ross Andrew

SPARK Symposium Presentations

Mercury contamination in aquatic ecosystems is a pressing environmental and public health concern, particularly in urban areas where industrial runoff and wastewater contribute to heavy metal accumulation. This study investigates mercury presence in fish from Richland Creek in Nashville, TN, by analyzing histological changes in liver and muscle tissues. Mercury bioaccumulates in aquatic food chains, potentially leading to physiological damage in fish and posing health risks to humans who consume contaminated seafood. While prior research has established mercury’s toxic effects, there is a need for localized studies assessing its presence in urban waterways. The hope is to find histological abnormalities …

Lead Bioaccessibility And Commonly Measured Soil Characteristics (Detroit, Mi, Usa) Phase Ii, Conor T. Gowan, Sabrina R. Good, Allison R. Harris, Patrick Crouch, Shawn P. Mcelmurry

Open Data at Wayne State

Urban soil contaminated with anthropogenic sources of Pb is a major contributor to child Pb exposure. To assess the Pb risk in urban areas, composite samples were collected from 142 voluntary privately owned 142 residential parcels in Detroit, Hamtramck, and Highland Park, Michigan. Samples were collected at two time periods, before and after treatment applied for those denoted as treatment sites. Samples were collected from areas covered with turf grass on the parcels from the front, middle and rear sections. Soils were collected with a bulb planter at approximately 10cm depth and were cleaned with a tap water-Liquinox detergent solution …

Potentiation Of Gelonin Cytotoxicity By Pulsed Electric Fields, Olga N. Pakhomova, Eleni Zivla, Giedre Silkuniene, Mantas Silkunas, Andrei G. Pakhomov

Bioelectrics Publications

Gelonin is a ribosome-inactivating protein with extreme intracellular toxicity but poor permeation into cells. Targeted disruption of cell membranes to facilitate gelonin entry is explored for cancer and tissue ablation. We demonstrate a hundreds- to thousands-fold enhancement of gelonin cytotoxicity by pulsed electric fields in the T24, U-87, and CT26 cell lines. The effective gelonin concentration to kill 50% of cells (EC₅₀) after electroporation ranged from <1 nM to about 100 nM. For intact cells, the EC₅₀ was unattainable even at the highest gelonin concentration of 1000 nM, which reduced cell survival by only 5–15%. For isoeffective electroporation treatments using 300 ns, 9 µs, and 100 µs pulses, longer pulses were more efficient at lowering gelonin EC₅₀. Increasing the electric field strength of 8, 100 µs pulses from 0.65 to 1.25 kV/cm reduced gelonin EC₅₀ from 128 nM to 0.72 nM. Conversely, the presence of 100 nM gelonin enabled a more than 20-fold reduction in the number of pulses required for equivalent cell killing. Pulsed electric field-mediated delivery of gelonin shows promise for hyperplasia ablation at concentrations sufficiently low to minimize or avoid systemic toxicity.

Evaluation Of The Dnazyme Gr5 For The Determination Of Lead Speciation In Natural Waters, Gaganprit Gill

Theses and Dissertations (Comprehensive)

This thesis explores the development and application of a DNAzyme-based biosensor designed to detect labile metal species in environmental samples. Real time and on-site monitoring of labile metal fractions would make a valuable contribution to environmental management, as these fractions are the most bioavailable and pose significant toxicity risks to aquatic organisms. Conventional methods for detecting labile metals, while effective, are often burdened by high costs, complexity, and lengthy processing times, making them less ideal for rapid and widespread environmental assessments.

The first manuscript of this thesis (chapter 2) establishes the fundamental capabilities of the Pb²⁺-specific DNAzyme GR5 …

Effects Of Round-Up On The Environment, Sandra J. Marcu

Journal of Earth and Life Science

Many people around the world have used and still currently use Roundup but are unaware of the effects it has on the environment. Roundup is a spray on application weedkiller that is widely used around the world today both residentially and commercially. It enables its user to grow a garden or a field of crops with a no-tilling approach to eliminate weeds. It is a well-known and popular choice for killing weeds that has been around since the mid 1970’s (Oca, 2017). John Franz, a Monsanto scientist discovered that glyphosate (main ingredient in Roundup) was an herbicide or weedkiller, and …

Decoding Tattoo And Permanent Makeup Pigments: Linking Physicochemical Properties To Absorption, Distribution, Metabolism, And Elimination Profiles Using Quantitative Structure-Activity Relationship (Qsar)-Based New Approach Methodologies (Nams), Girija Bansod, Ajay Vikram Singh, Preeti Bhardwaj, Tulika Rai, Sweta Vijay Nakhale, Amruta Shelar, Rajendra Patil, Peter Laux, Andreas Luch, Christopher J. Osgood, Michael W. Stacey

Biological Sciences Faculty Publications

The safety and quality of tattoo and permanent makeup (PMU) pigments are subject to increased scrutiny due to their potential to cause adverse effects like anaphylaxis, photoallergic responses, and long-term toxicity. These undesirable reactions governed by their chemical structure possess varied physicochemical properties and absorption, distribution, metabolism, and elimination (ADME) characteristics. These properties control the pigment behavior during application, stability, and interaction with human tissue. The correlation between these physicochemical characteristics and ADME parameters of tattoo/PMU pigments remain under-explored despite the current advances in toxicology. Our study aims to address and bridge the gap by leveraging open-access QSAR computational toxicology …

Impact Of Tetrahydrocannabinol (Thc) On Daphnia Magna Heart Rate, Ashley Cosgrave

Williams Honors College, Honors Research Projects

Marijuana (Cannabis) is currently federally illegal within the United States and classified as a Schedule I drug. This leaves a large research gap on the impacts of Tetrahydrocannabinol (THC) use. Daphnia magna are frequently used as a model organism for the human heart and toxicology screenings due to their myogenic heart, similarities in physiological pathways, and sensitivity to toxins. As such, in order to bridge the research gap and uncover potential use of Daphnia magna as a model organism for humans in regard to impact on heart rate, we hypothesized that if Daphnia magna possess CB1 receptors or an equivalent …

Environmental Pollution And Early-Life Metabolic Programming, Lisa Koshko

Wayne State University Dissertations

Substantial evidence demonstrates that parental pollutant exposures can induce harmful health effects in the offspring, including the predisposition to Type II Diabetes. As rates of Type II Diabetes continue to rise in younger populations, a crucial gap lies in understanding the role of parental influence in the etiology of later-life metabolic disease. Therefore, the central goal of this work was to determine how early life exposure to smoking level benzene, an endocrine-disrupting air pollutant, affects the metabolic health of offspring, and to identify potential developmental mechanisms involved in disease susceptibility. This goal was achieved using two models of early life …

Évaluation Et Caractérisation De L'Exposition Aux Fumées De Soudage Et Leurs Composantes Métalliques Lors D'Activités De Soudage Au Québec, Michèle Bouchard, Jairo Buitrago-Cortes, Naïma El Majidi, Jonathan Côté, Denis Dieme, Marc Mantha, Philippe Sarazin, Capucine Ouellet, Loïc Wingert

Rapports de recherche scientifique

Problématique et objectifs :

Les fumées de soudage sont classées comme cancérogènes chez l’humain et sont associées à un risque accru de plusieurs autres effets sur la santé des soudeurs. L’objectif général de cette recherche était d’établir la nature et le niveau d’exposition aux composantes métalliques lors d'activités de soudage chez des apprentis soudeurs au Québec, en effectuant des mesures dans différentes matrices biologiques et dans l’air lors d’un suivi longitudinal.

Méthode :Cette recherche a été réalisée dans des écoles d'apprentis soudeurs de la région de Montréal, où les techniques de soudage les plus courantes sont utilisées. Elle a …

Investigating Plk1 In Pulmonary Fibrosis, Tempany Arbogast

Theses and Dissertations--Toxicology and Cancer Biology

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease, with a median survival of only 2–3 years following diagnosis. In the United States, the disease contributes to more than 40,000 deaths annually, underscoring its severe clinical burden. Alveolar type II (AT2) lung epithelial cells serve as progenitors that maintain alveolar integrity by replenishing epithelial populations and producing surfactants, while fibroblasts and myofibroblasts regulate the extracellular matrix and structural support. In pulmonary fibrosis (PF) injury to AT2 cells promotes cytokine and growth factor release, driving inflammation, fibroblast proliferation, myofibroblast accumulation, and excessive extracellular matrix deposition. Aberrant AT2 cell …

Cannabinoid-2 Receptor Activation Attenuates Sulfur Mustard Analog 2-Chloroethyl-Ethyl-Sulfide-Induced Acute Lung Injury In Mice, Gregory Nicholson, Nicholas Richards, Janette Lockett, My Boi Ly, Raj V. Nair, Woong-Ki Kim, K. Yaragudri Vinod, Nagaraja Nagre

Department of Biomedical and Translational Sciences Faculty Publications

Background: Exposure to sulfur mustard (SM; 2,2′-dichlorodiethyl sulfide) causes toxicity in the human body, particularly the lungs. The molecular mechanisms of SM-induced lung damage are elusive, and no effective treatments exist. This study explores the anti-inflammatory potential of cannabinoid receptor 2 (CB2R) activation in mitigating acute lung injury (ALI) and inflammation induced by 2-chloroethyl ethyl sulfide (CEES), a structural analog of SM. Methods: C57BL/6J mice were exposed to CEES via intratracheal administration to model ALI. CB2R activation was achieved through the intraperitoneal administration of HU308, a selective synthetic agonist. ALI and inflammation were evaluated at 48 h post-exposure to CEES. …

Developing A Simplified Method Of Measuring Ultrafine Particulate Matter Dose Concentrations For Diesel Emissions, Nafisat Ohunene Isa

Graduate Theses, Dissertations, and Problem Reports (ETD)

Abstract

Developing a Simplified Method of Measuring Ultrafine Particulate Matter Dose

Concentrations for Diesel Emissions

Ultra-fine particulate matter (UFP), particularly from diesel emissions, poses significant health and environmental risks due to its small size and potential to penetrate deep into the respiratory system. Accurate measurement of UFP concentrations is essential for assessing exposure and mitigating health impacts. However, current methods for measuring UFP can be complex, time-consuming, and costly. This study aims to develop a simplified method for efficiently measuring UFP concentrations from diesel emissions, which will enable easier and more widespread monitoring of air quality and public health impacts. …

Treatment Of Myocardial Infiltration Of Hodgkins Lymphoma: A Catch-22, Jennifer Priessnitz, Erin Biringen, Fadi Khoury, Christina Bergin

Department of Medicine Faculty Publications

Background: Cardiac sequelae in Hodgkin Lymphoma (HL) can manifest as involvement of the heart and pericardium. Direct cardiac involvement is rare, and myocardial infiltration is distinctly unusual.¹ When it does occur, it is often a late manifestation of lymphoma, with a median onset of 20 months after initial diagnosis, and it is usually associated with advanced-stage disease.²

Case: A 34-year-old male was diagnosed with classic HL by lymph node biopsy. During his hospitalization, the patient remained in sinus tachycardia with heart rate up to 150 with no dysrhythmias. Transthoracic echocardiogram (TTE) revealed a reduced ejection fraction (EF) of 36% concerning …

Naloxone Prescribing At Hospital Discharge: A Quality Improvement Initiative, Timothy Ford

Doctors of Nursing Practice (DNP) Final Projects, 2020-current

Opioid overdose deaths remain one of the largest public health challenges in the United States. Naloxone allocation is an important tool to help combat opioid overdose deaths. The literature supports that hospitalized patients are generally receptive to receiving naloxone and opioid education and interdisciplinary teams working together can help facilitate identification of high-risk patients for naloxone allocation. This quality improvement change, guided by the IHI Triple Aims and Model for Healthcare Improvement frameworks, sought to increase the rate of patients leaving the Hospital Medicine Service with naloxone. To accomplish this, during the target units’ daily interdisciplinary rounds, providers were prompted …

Low Concentrations Of Hexavalent Chromium In Drinking Water Induce Alzheimer’S Disease Neuropathology: Using A Toxic Aging Coin Approach To Assess Hexavalent Chromium Neurotoxicity, Liam Buchanan, Samuel Vielee, Spencer Roof, Haiyan Lu, Jamie L Young, Idoia Meaza Isusi, Aggie Williams, Joseph Kouokam, Sandra Wise, Luping Guo, Jun Cai, John Wise, John P. Wise Jr.

The Cardinal Edge

Introduction: We are currently facing an aging crisis, as 20% of the U.S. population will be geriatric (65+) by 2030. This growing geriatric population will result in increasing prevalence of age-related diseases, coinciding with increasingly prevalent environmental pollution. Environmental pollution is a ubiquitous health threat that affects people at all ages and contributes to aging pathology. However, geriatric individuals are likely more susceptible to the negative health effects from environmental pollution. The distinct effects of environmental pollutants across age groups are currently understudied. We use a Toxic Aging Coin approach to investigate: 1) how age impacts toxicity (heads), …

Anti-Aging Properties Of Cosmetics, Anna Lipinski

The Cardinal Edge

It is well established that external factors, specifically UV exposure, are among the highest contributors to the biological aging of the skin. Prolonged exposure may disrupt skin cell homeostasis through shifts in proteostasis, accumulation of reactive oxidative species, premature cellular senescence, and inflammatory pathways. Cosmetic companies have responded to this by producing products marketed as "youthful" and "anti-aging" by including specific compounds into formulas to combat skin aging. This review discusses the specific mechanisms of anti-aging formulas, including polyphenols as senotherapeutic agents and L-ascorbic acid as an anti-inflammatory compound, in resisting the biological aging of the skin.