Changes In Morphology Structure Research Articles

Photodegradation Processes and Weathering Products of Microfibers in Aquatic Environments.

Microplastics, particularly microfibers (MFs), pose a significant threat to the environment. Despite their widespread presence, the photochemical reactivity, weathering products, and environmental fate of MFs remain poorly understood. To address this knowledge gap, photodegradation experiments were conducted on three prevalent MFs: polyester (POL), nylon (NYL), and acrylic (ACR), to elucidate their degradation pathways, changes in surface morphology and polymer structure, and chemical and colloidal characterization of weathering products during photochemical degradation of MFs. The results showed that concentrations of dissolved organic carbon, chromophoric dissolved organic matter (DOM), and fluorescent components consistently increased during weathering, exhibiting a continuous release of DOM. Scanning electron microscopy and Raman spectroscopy revealed changes in the surface morphology and polymer spectra of the MFs. During the weathering experiments, DOM aromaticity (SUVA254) decreased, while spectral slope increased, indicating concurrent DOM release and degradation of aromatic components. The released DOM or nanoplastics were negatively charged with sizes between 128 and 374 nm. The production rate constants of DOM or the photochemical reactivity of MFs followed the order ACR > NYL ≥ POL, consistent with their differences in chemical structures. These findings provide an improved understanding of the photochemical reactivity, degradation pathways, weathering products, and environmental fate of microfibers in the environment.

CuxS films as photoelectrodes for visible-light water splitting

Copper sulfides are appealing semiconductors for optoelectronics applications requiring visible-light activity, such as solar water splitting, due to their relatively low band gaps and earth-abundance. This study investigates the effect of deposition conditions, including substrate temperature and background gas pressure, on the characteristics and photoelectrochemical performance of copper sulfide (CuxS) films grown by pulsed laser deposition (PLD) on Si (100) substrates. The results reveal that varying the deposition parameters influences the crystalline phases, morphology, and optoelectronic properties of the films. For deposition at room temperature, the films exhibited covellite CuS phase, while elevated deposition temperatures (250 °C and 500 °C) led to the formation of Cu1.8S and Cu2S phases, resulting in narrowing of the band gap, with the increased temperature also enhancing the film crystallinity and surface roughness. As a result of the changes in film morphology and crystal structure, photocurrent density magnitudes increased with higher deposition temperatures, reaching 0.747 mA/cm2 at −0.8 V for films deposited at 500 °C under vacuum, at least an order of magnitude higher than reported in comparable previous studies of the photoelectrochemical performance of CuxS. Background gas pressure only slightly affected the photocurrent density, with changes in photoactivity also correlating with changes in film roughness and band gap. The results demonstrate the good visible-light activity and behavior of CuxS as a stand-alone photoelectrode material, with tunability based on the fabrication conditions, suggesting their potential use in photoelectrochemical and other solar energy conversion applications.

Toward Sustainable Olefins: Electroreduction of CO2 to Multi-Carbon Olefins Using Trimetallic Cu-Rich Catalysts

The sustainable conversion of carbon monoxide (CO2) into value-added chemicals via electrochemical methods, powered by renewable electricity, is considered as a promising approach to meet the global energy demand and close the anthropogenic carbon cycle. However, this technology is in the early stage of development, particularly in the production of multi-carbon (C2+) hydrocarbons due to well-studied thermodynamic and kinetic barriers. To overcome these challenges, developing a catalyst with high activity and selectivity is crucial to minimize energy input and maximize the effectiveness of C2+ products formation.In this work, we will present our recent advancement on developing non-precious tri-metallic catalysts with copper-rich surface synthesized by our developed atomically controllable and environmentally friendly synthesis method. The developed nanostructured tri-metallic electrocatalysts by this method show remarkable selectivity and activity in the electrochemical conversion of CO2 to olefins. In particular, our electrochemical results show an overall C2+ olefine Faradaic efficiency (FE%) of 69% more specifically 58% ethylene and 11% propylene at a current density of -112 mA/cm² under applied potential of -2.8 V in an anion exchange membrane (AEM) electrolyzer. To gain a better understanding of the catalytic performance and find a structural-performance relationships for the developed materials, we performed several physicochemical and electrochemical characterization experiments, including X-ray diffraction (XRD), scanning transmission electron microscopy (STEM), and X-ray photoelectron spectroscopy (XPS). We will discuss morphology and atomic structure changes of the developed materials under realistic conditions, with a specific focus on understanding how different trimetallic interfaces influence selectivity and activity in the electrochemical CO2 reduction reaction (eCO2RR).

Evaluation of the Relationship Between Osteoarthritis and Morphological Changes in the Joint Structures in Temporomandibular Disorders By Cone Beam Computed Tomography

Evaluation of the Relationship Between Osteoarthritis and Morphological Changes in the Joint Structures in Temporomandibular Disorders By Cone Beam Computed Tomography

Hydrolysis of Babool wood biomass using carbocation scavengers assisted ionic liquid pretreatment for the production of sugars and furfurals

The present study highlights the performance of carbocation scavengers for the pretreatment of hardwood biomass followed by the production of bio-based products. The behaviour of different carbocation scavengers namely; 2-Napthol, 4 Hydroxybenzoic acid, Vanillic acid, Catechol, Hydroquinone, Resorcinol and Phenol and their mitigating effect on the rate of hydrolysis was explored under different operating conditions. All the carbocation scavengers show significant changes in the crystallinity index leading to distinct morphological and physiochemical changes in the biomass structure. Results revealed that the addition of carbocation scavengers not only reduces the inhibitory effect of structured lignin but also enhances the accessibility of cellulose and hemicellulose and facilitates the production of sugars and 5-Hydroxymethyl Furfural. Maximum 5-HMF yield was observed using 2-Napthol at an optimised concentration of 2 wt% (1.5 mL) at 190 °C in 60 min. Further, to evaluate the effect of acetyl groups, biomass deacetylation was also performed. The highest deacetylation effect was observed at 170 °C and showed ∼73% and ∼94% reduction in the holocellulosic content in 60 min. The proposed study develops a sustainable and viable route to suppress the inhibitory effect of lignin with the utilization of carbocation scavengers and enhances biomass digestibility that favours the production of bio-based chemicals.

Degradation Behaviors of Polylactic Acid, Polyglycolic Acid, and Their Copolymer Films in Simulated Marine Environments.

Poly(lactic acid) (PLA) and poly(glycolic acid) (PGA) are extensively studied biodegradable polymers. However, the degradation behavior of their copolymer, poly(lactic-co-glycolic acid) (PLGA), in marine environments has not yet been confirmed. In this study, the changes in macroscopic and microscopic morphology, thermal properties, aggregation, and chemical structure of PLA, PGA, PLGA-85, and PLGA-75 (with 85% and 75% LA content) in simulated marine environments were investigated. Results revealed that degradation occurred through hydrolysis of ester bonds, and the degradation rate of PGA was faster than that of PLA. The amorphous region degraded preferentially over the crystalline region, leading to cleavage-induced crystallization and decreased thermal stability of PLA, PLGA-85, and PLGA-75. The crystal structures of PLGAs were similar to those of PLA, and the higher GA content, the faster was the degradation rate. This study provides a deeper understanding of the seawater degradation behaviors of PLA, PGA, and their copolymers, and provides guidance for the preparation of materials with controllable degradation performance.

Biodegradation behavior of poly (glycolic acid) (PGA) and poly (butylene adipate-co-terephthalate) (PBAT) blend films in simulation marine environment

Polyglycolic acid (PGA) and poly (butylene adipate-co-terephthalate) (PBAT), as widely applied biodegradable polymers, the degradation behavior of their blends in marine environments has not been proven. This study investigated the changes of macroscopic and microscopic morphology, thermal properties, crystalline and chemical structure, degradation rate of PGA/PBAT blends with different ratios in the simulation marine environment containing sediments and marine organisms. The results showed that degradation primarily occurred due to ester bond breakage, and PGA exhibited a faster degradation rate than PBAT films. The amorphous region degraded more rapidly than the crystalline region, and the thermal stability of the materials decreased. The degradation of PGA and PBAT blends followed their respective single degradation laws and the compatibility of blend samples decreased after degradation. The degradation rate of the samples was obtained by measuring the biochemical oxygen demand, which indicated that a higher PGA content could result in a faster degradation rate for PGA/PBAT films. This study provides an efficient method for constructing materials with controlled biodegradability.

Defect engineering of copper-doped mesoporous manganese dioxide nanoflowers for enhancing electrocatalytic detection of hydrogen peroxide

Birnessite-type δ-MnO2 nanoflowers doped with copper ions (Cu-MnO2) can enhance the catalytic performance of MnO2-based catalysts for efficient electrochemical sensing of H2O2. There are no significant changes in the surface morphology and lattice structure of bulk MnO2 after Cu doping via engineered cation exchange. The catalytic Cu species are effectively incorporated into the tunnel entrance of δ-MnO2, the Mn site in the MnO6 octahedron, and surface defects. The Cu doping enhances the electrical and ionic conductivities, and generates numerous Mn3+ defects, oxygen vacancies, and Cu+/Cu2+ redox sites. Thus, the Cu doping facilitates the transport and adsorption of more H2O2 molecules to the catalytic sites, significantly increasing the catalytic rate. In contrast, pristine MnO2 exhibits negligible catalytic performance for H2O2 reduction because of its slow catalytic kinetics and low electrical conductivity. The Cu-MnO2 catalyst exhibits higher sensitivity (105.7 μA·mM−1·cm−2), a lower detection limit (0.6 μM), and a broader linear range (0.005 ∼ 4.2 mM) compared to pristine δ-MnO2.

Role of electrochemical cell configuration on the selectivity of CuZnAl-oxide-based electrodes for the continuous CO2 conversion: aqueous electrolyte vs. catholyte-less configuration

This research is a significant step forward in understanding how the electrochemical cell setup influences CO2 conversion. The performance of Cu–Zn–Al metal oxide-based catalysts was compared in two reactor configurations: a gas diffusion electrode (GDE) cell with an aqueous electrolyte and a Membrane Electrode Assembly (MEA) cell operating in the gas phase without catholyte. The different operations induced significant morphological and crystalline structural changes, profoundly impacting the catalytic behaviour. The MEA configuration, for instance, led to the formation of a higher Cu0/Cu1+ ratio in the catalysts, promoting C–C coupling for C2H4 production. Conversely, the GDE operation favoured alcohol (ethanol and methanol) production by balancing copper oxidation states formed in situ in the presence of the aqueous catholyte. Zn and Al oxides also played a role in stabilising the resulting Cu species, some of which remained oxidised on the electrode surface. These findings underscore the crucial influence of varying cell operation conditions on catalyst reconstruction, shaping the quantity of Cu0 + Cu1+ species formed in situ to tailor catalyst selectivity.

Detection of morphological changes in the Turkish hump structure in hyperprolactinemia caused by taking oral contraceptives

Detection of morphological changes in the Turkish hump structure in hyperprolactinemia caused by taking oral contraceptives

Cortical and subcortical structural changes in pediatric patients with infratentorial tumors.

This study aimed to detect supratentorial cortical and subcortical morphological changes in pediatric patients with infratentorial tumors. The study included 24 patients aged 4-18 years who were diagnosed with primary infratentorial tumors and 41 age- and gender-matched healthy controls. Synthetic magnetization-prepared rapid gradient echo images of brain magnetic resonance imaging were generated using deep learning algorithms applied to T2-axial images. The cortical thickness, surface area, volume, and local gyrification index (LGI), as well as subcortical gray matter volumes, were automatically calculated. Surface-based morphometry parameters for the patient and control groups were compared using the general linear model, and volumes between subcortical structures were compared using the t-test and Mann-Whitney U test. In the patient group, cortical thinning was observed in the left supramarginal, and cortical thickening was observed in the left caudal middle frontal (CMF), left fusiform, left lateral orbitofrontal, left lingual gyrus, right CMF, right posterior cingulate, and right superior frontal (P < 0.050). The patient group showed a volume reduction in the pars triangularis, paracentral, precentral, and supramarginal gyri of the left hemisphere (P < 0.05). A decreased surface area was observed in the bilateral superior frontal and cingulate gyri (P < 0.05). The patient group exhibited a decreased LGI in the right precentral and superior temporal gyri, left supramarginal, and posterior cingulate gyri and showed an increased volume in the bilateral caudate nucleus and hippocampus, while a volume reduction was observed in the bilateral putamen, pallidum, and amygdala (P < 0.05). The ventricular volume and tumor volume showed a positive correlation with the cortical thickness in the bilateral CMF while demonstrating a negative correlation with areas exhibiting a decreased LGI (P < 0.05). Posterior fossa tumors lead to widespread morphological changes in cortical structures, with the most prominent pattern being hypogyria. This study illuminates the neurological impacts of infratentorial tumors in children, providing a foundation for future therapeutic strategies aimed at mitigating these adverse cortical and subcortical changes and improving patient outcomes.

Эффекты воздействий радиочастотных электромагнитных полей на нервную систему. Эксперименты in vitro (обзор)

The effects of mobile communications on the population, primarily on children and adolescents as the cohort most vulnerable to any environmental factors, dictates the need for a thorough investigation into the impact of radio frequency electromagnetic fields (RF EMF) on the central nervous system (CNS) as the main target of their action. In this regard, the analysis of experimental data as an indirect assessment of possible negative changes in the body of young animals under the influence of RF EMF, including 5G and Wi-Fi, is highly relevant. We performed a systematization of experimental data, which will be presented in two parts: in vitro and in vivo experiments. This article introduces materials indicating both diversity of approaches to studying the effects of RF EMF on the central nervous system and difficulties of systematizing the results of the experiments. The analysis of literature data showed that, despite the numerous studies into the effects of RF EMF in vitro, CNS cell cultures are used rather rarely. However, this paper examines in detail the results of in vitro experiments: changes in the action potential, morphological changes in cells and the myelin sheath, and changes in the permeability of the blood–brain barrier (using cultures of only nerve cells). It was established that, despite some inconsistency in the results obtained, most studies indicate a negative effect of RF EMF on CNS cells. The morphological and histological changes in CNS structures under the influence of RF EMF will be presented in the next part of the review.

Renal calcium and magnesium handling during pregnancy: modeling and analysis.

Pregnancy is associated with elevated demand of most nutrients, with many trace elements and minerals critical for the development of fetus. In particular, calcium (Ca2+) and magnesium (Mg2+) are essential for cellular function, and their deficiency can lead to impaired fetal growth. A key contributor to the homeostasis of these ions is the kidney, which in a pregnant rat undergoes major changes in morphology, hemodynamics, and molecular structure. The goal of this study is to unravel the functional implications of these pregnancy-induced changes in renal handling of Ca2+ and Mg2+, two cations that are essential in a healthy pregnancy. To achieve that goal, we developed computational models of electrolyte and water transport along the nephrons of a rat in mid and late pregnancy. Model simulations reveal a substantial increase in the reabsorption of Mg2+ along the proximal tubules and thick ascending limbs. In contrast, the reabsorption of Ca2+ is increased in the proximal tubules but decreased in the thick ascending limbs, due to the lower transepithelial concentration gradient of Ca2+ along the latter. Despite the enhanced transport capacity, the marked increase in glomerular filtration rate results in elevated urinary excretions of Ca2+ and Mg2+ in pregnancy. Furthermore, we conducted simulations of hypocalcemia and hypomagnesemia. We found that hypocalcemia lowers Ca2+ excretion substantially more than Mg2+ excretion, with this effect being more pronounced in virgin rats than in pregnant ones. Conversely, hypomagnesemia reduces the excretion of Mg2+ and Ca2+ to more similar degrees. These differences can be explained by the greater sensitivity of the calcium-sensing receptor (CaSR) to Ca2+ compared with Mg2+.NEW & NOTEWORTHY A growing fetus' demands of minerals, notably calcium and magnesium, necessitate adaptations in pregnancy. In particular, the kidney undergoes major changes in morphology, hemodynamics, and molecular structure. This computational modeling study provides insights into how these pregnancy-induced renal adaptation impact calcium and magnesium transport along different nephron segments. Model simulations indicate that, despite the enhanced transport capacity, the marked increase in glomerular filtration rate results in elevated urinary excretions of calcium and magnesium in pregnancy.

Quantitative image analysis for assessing extracellular polymeric substances in activated sludge under atrazine exposure

Extracellular polymeric substances (EPS) play a vital role in biological wastewater treatment systems. This study investigates the impact of herbicide atrazine (ATZ) on the overall performance, EPS yield, composition, and sludge morphology in an activated sludge (AS) system operated in a sequencing batch reactor (SBR). Since conventional methods for analyzing EPS are time-consuming and releases residues, a new approach was developed in this work to evaluate the EPS fractions and components, based on the morphological characterization of the biomass using quantitative image analysis (QIA) technique coupled with multivariate statistics.Results showed that exposure to ATZ inhibit biomass activity in terms of organic matter (COD) and nitrogen removal. Moreover, both tightly bound EPS (TB-EPS) and loosely bound EPS (LB-EPS) increased under ATZ, indicating that microorganisms release EPS as a defense mechanism against environmental changes. The PN/PS ratio also increases, indicating likely increased hydrophobicity in ATZ phases. Furthermore, ATZ phases exhibit a predominance of large aggregates compared to intermediate and small ones, indicating a change in aggregate morphological structure associated with EPS production. The new approach using QIA coupled with partial least squares (PLS) modeling provides accurate predictions of EPS content. The increase in TB-EPS is closely related to the rise of large aggregates in phases exposed to higher ATZ concentrations. The PLS models demonstrate high accuracy for EPS prediction (coefficients of determination, R2 above 0.86), showcasing the feasibility of using QIA for EPS assessment in AS systems. This approach offers significant potential for regular process monitoring and management, providing a more environmentally friendly methodology by eliminating the need for chemical usage.

Comprehending the surface melt characteristics, calving processes, and seasonal ice velocity of Dålk glacier in Larsemann Hills, East Antarctica

Surface melting induces hydro-fracturing and deformational changes on the ice surface, which have a substantial impact on its dynamics and stability and therefore, comprehending these processes is crucial for ice sheet mass balance and stability. The present study is an attempt to understand the surface melt characteristics, seasonal ice movement, and calving processes of the Dålk glacier located in the Larsemann Hills of East Antarctica using multi-sensor remote sensing observations from 2017 to 2023. We identified and examined several melt features across the glacier and analysed their evolution during the study period. Frontal changes, calving events, and seasonal surface ice velocities of the glacier were also investigated during the study period. We found that the evolution and drainage of the melt features over the Dålk glacier is highly dynamic in nature with a significant inter-annual variability. We report substantial morphological changes in the ice doline structure that may be driven by the surface melt patterns, ice movement, and ice deformation in the region which also, affect the drainage of the nearby connected melt ponds and features. Several minor to very major calving events observed during the period due to immense disintegration processes during the preceding melting season that also affected the ice movement. We also highlight the need of monitoring and studying such melt features over the outlet glaciers that concerns the imminent catastrophic fragmentation and deformational changes over the glacier.

Pathomorphological and immunohistochemical characteristics of the testicle in children with critical ischemia during acute torsion

Background. The occurrence of acute torsion of the testicle in children leads to ischemia of the testicle, and in the absence of timely medical assistance - to the loss of the organ. The period from 12 hours to 24 hours from the onset of the disease leaves only a 20% chance of saving the genital gonad. There are still no exact signs of viability of the affected gonad in case of critical ischemia of the testicle due to its torsion. Therefore, the study of the dynamics of changes in morphological structures in the course of acute testicular torsion, morphological and functional disorders resulting from torsion, is of great practical interest, because there is no consensus on the nature and degree of these changes in the affected gonad. Objective: study of the nature and severity of pathomorphological changes and immunohistochemical features of the acute torsion testicle in children within 12.1-24 hours or more from the onset of the disease. Methods. A histological, histochemical, and immunohistochemical study of testicular tissue biopsies taken during the operation of detorsion and orchiopexy, and orchidectomy within 12.1–24 hours or more from the onset of clinical symptoms of acute unilateral torsion in 16 patients was conducted. Results. The morphological study of the gonads showed that the duration of acute torsion of 12.1–24 hours or more is characterized by severe pathological changes found in the testicles. After 18 hours of acute ischemia, tubules were visualized in many fields of view in the form of shadows with the impossibility of identifying the structures due to hemorrhagic or ischemic infarcts. Immunohistochemical typing demonstrated the absence of expression of vimentin and calretinin, which indicated the death of sustentocytes (Sertoli cells) and Leydig cells. With a duration of acute torsion of 12.1-18 hours, a histochemical study of glycogen in the cytoplasm of spermatogonia, spermatocytes, and sustentocytes using the PAS-reaction showed that some cells of the spermatogenic epithelium were characterized by irreversible changes preceding necrosis, although giant multinucleated spermatids with relatively preserved glycogen, which meant there was a minimal chance for saving the gonad. Conclusion. Total duration of symptoms and degree of male gonadal torsion are the main prognostic factors for testicular preservation or necrosis in episodes of torsion. The duration of an acute torsion of 12.1-18 hours, according to morphological research, leaves in 42,9% of cases the presence of a minimal chance of saving the genital gonad. After 18 hours from the onset of acute complete testicular torsion in children, the operation of choice is orchidectomy.

Pressure-induced structural modifications of imogolite nanotubes and of their methylated analogues

Structural modifications of single-walled aluminosilicate clay nanotubes have been studied under hydrostatic pressure by in situ synchrotron X-ray scattering. Imogolite nanotubes (INT) of nominal composition (OH)3Al2O3SiOH, and methyl-modified imogolite nanotubes (m-INT), (OH)3Al2O3SiCH3, have hydrophilic and hydrophobic internal cavities, respectively. Nanotube chiralities also differ, with zigzag (INT) and armchair (m-INT) chirality. In this work, pressure-induced changes in nanotube morphology and atomic structure are studied as a function of chirality, affinity of the inner cavity, and the pressure-transmitting medium used. Radial deformation and collapse of nanotubes are evidenced below 3 GPa, followed by the formation of a lamellar phase at higher pressures. In the case of INT, the collapse pressure value depends on the pressure transmitting medium chosen. Axial compressibility is measured, and a pseudo Young's modulus Y is determined to be equal to ∼265 GPa for INT and below 80 GPa for m-INT, underpinning the role of nanotube chirality in mechanical properties.

Effects of copper and bismuth dopants on PVA/NBT film as an X-ray dosimeter

Low-dose X-rays in the order of milligrays (mGy) are employed in diagnostic radiology. This poses a challenge, considering commercially used dosimeters have limitations in detecting low-dose X-rays. Accordingly, the goal of this research was to fabricate a nitro blue tetrazolium-doped polyvinyl alcohol (PVA/NBT) film dosimeter that could respond to low-dose X-rays while also investigating the effects of introducing copper(II) and bismuth(III) ions on the film's detecting ability. The films were synthesized by the solvent casting method and then exposed to X-ray radiation at doses in the range of 0–2.626 mGy. Optical density and UV–Vis transmittance measurements were carried out to identify changes in the film's optical characteristics brought on by X-ray radiation. In addition, changes in the film's surface morphology and chemical structure were examined by scanning electron microscopy (SEM) and FTIR spectroscopy. According to the results of the optical density measurement, introducing copper(II) ions to the film increased its sensitivity and response linearity. In contrast, the opposite was shown in the case of bismuth(III)-doped films. According to FTIR analysis, film X-ray irradiation caused the PVA to degrade. The development of grain structures on the film surface might be related to the reduction of the copper(II) and bismuth(III) ions. This study discovered that copper(II) ion-doped PVA/NBT film has promising low-dose X-ray detection properties.

PRODUCTION AND RESEARCH OF SORBENTS FROM FOOD PLANT WASTES FOR WATER PURIFICATION

The article describes the results of research on production of modified types of sorbents based on waste food plants and the possibility of drinking water purification from Ca2+ and Mg2+ ions. Sunflower and buckwheat wastes widely spread in the East Kazakhstan region were selected for production of modified sorbent. Structural features of sunflower and buckwheat shells were studied. It was found that samples of the initial form of buckwheat and sunflower, washed with distilled water, consist of very dense and small micropores. It was found that the surface of the sorbents particles is changed by washing with alcohol solution, with pores and hillocks appearing on the surface of sunflower husk particles. In acid-base-treated sorbents, an increase in the number of macropores and a change in the general morphological structure are observed. As a result of defining the sorption capacity of sorbents produced by acid-alkaline activation, it is on average 0.06 mg/g in iodine and 1.3 mg/g in methylene blue higher than that of medical activated carbon. The results of materials sorption capacity study produced from sunflower husk, sequentially treated with 8.2% hydrochloric acid solution and 16,5% sodium hydroxide solution, indicated effect respect to Ca2+ and Mg2+ ions showed a high purification effect of 98.7% and 95.8%, respectively. The above-mentioned modified sorbent is proposed as a sorption material in the production of filters for drinking water purification.

Abstract 1463: Characterizing inflammation-induced epigenetic and transcriptomic alterations driving NSCLC using lung organoid models

Abstract Chronic inflammation is a major driver of lung cancer and contributes to its pathogenesis by inducing genetic and epigenetic alterations. These, in turn, modulate the microenvironment to facilitate emergence of tumor promoting immune evasive mechanisms. The evolution of epigenetic events and their role, both alone, and in association with lung cancer specific genetic drivers in initiation of lung cancer is not well delineated. Specific pathological subtypes of non-small cell lung cancer (NSCLC) have distinct cells of origin, suggestive of cell type-specific changes in driving their development. We employed lung organoid models with chronic exposure to cigarette smoke condensate (CSC) to elucidate sequential, cell type-specific epigenetic and transcriptomic alterations and their role in co-operating with genetic events to drive development of NSCLC. We examined epigenomic and transcriptomic alterations over a 6-month exposure period by DNA methylation arrays, ATAC-seq, and RNA-seq. We observe that CSC exposure causes distinct morphological changes in organoid structure and composition, accompanied by an increase in proliferative potential. Using flow cytometry and immunofluorescent staining approaches, we demonstrate a chronic inflammation-driven shift in stem cell populations accompanied by reduction in differentiated cell types. Bulk and single-cell RNA sequencing approaches identified distinct temporal changes in transcriptional signatures in CSC exposed organoids suggestive of evolution of an immune evasive and pro-tumorigenic phenotype. Gene set enrichment analysis revealed a downregulation of interferon signaling and upregulation of Myc targets and oxidative phosphorylation pathways in CSC treated organoids. Notably, co-culturing organoids with key immune cell populations, demonstrate the ability of the CSC exposed organoids to modulate shifts in immune cells from a pro- to anti- inflammatory state. In accordance with this shift in immune cell phenotype, CSC treated organoids secreted decreased levels of pro-inflammatory cytokines as measured by multiplex ELISA assays. Genome wide DNA methylation analysis reveal that CSC methylated genes were associated with differentiation and cell fate commitment as well as transcription factor activity. Finally, we demonstrate that introduction of key NSCLC-specific driver events at the 6-month time point sensitize only CSC treated organoids to tumor formation in vivo, leading to the development of distinct genetic driver-specific subtypes of NSCLC. Altogether, our results demonstrate the ability of chronic inflammation to drive key cell type-specific transcriptomic and epigenetic changes leading to the development of distinct subtypes of NSCLC. Our findings will help identify molecular correlates for early detection and aid development of novel therapeutic strategies for disease interception. Citation Format: Na Wang, Kara Lombardo, Raksha Padaki, Ray-Whay Chiu Yen, Malcolm V. Brock, Leslie Cope, Hariharan Easwaran, Stephen B. Baylin, Michelle Vaz. Characterizing inflammation-induced epigenetic and transcriptomic alterations driving NSCLC using lung organoid models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1463.