Alteration Products Research Articles

Dual Exposure to E-Cigarette Vapour and Cigarette Smoke Results in Poorer Airway Cell, Monocyte, and Macrophage Function Than Single Exposure.

E-cigarette users predominantly also continue to smoke cigarettes. These Dual Users either consume e-cigarettes in locations where smoking is not allowed, but vaping is, or to reduce their consumption of cigarettes, believing it will lead to harm reduction. Whilst it is known that e-cigarette vapour is chemically less complex than cigarette smoke, it has a distinct chemical profile, and very little is known about the health impacts of exposure to both chemical profiles vs. either alone. We simultaneously exposed cells in vitro to non-toxic levels of e-cigarette vapour extract (EVE) and cigarette smoke extract (CSE) to determine their effects on 16HBE14o- airway epithelial cell metabolism and inflammatory response, as well as immune cell (THP-1 cells and monocyte-derived macrophages (MDM) from healthy volunteers) migration, phagocytosis, and inflammatory response. We observed increased toxicity, reduced metabolism (a marker of proliferation) in airway epithelial cells, and reduced monocyte migration, macrophage phagocytosis, and altered chemokine production after exposure to either CSE or EVE. These cellular responses were greater after dual exposure to CSE and EVE. The airway epithelial cells from smokers showed reduced metabolism after EVE (the Switcher model) and dual CSE and EVE exposure. When EVE and CSE were allowed to interact, the chemicals were found to be altered, and new chemicals were also found compared to the CSE and EVE profiles. Dual exposure to e-cigarette vapour and cigarette smoke led to worse functional outcomes in cells compared to either single exposure alone, adding to limited data that dual use may be more dangerous than smoking only.

ROLE OF CYTOKINES IN PRE-ECLAMPSIA: A REVIEW

Preeclampsia is a serious and life-threatening pregnancy complication. Reduced uteroplacental perfusion and oxygen tension impaired trophoblastic differentiation and invasion altered placental production of immunomodulators and growth factors are all considered important aspects of the aetiology of the condition. The placenta expresses a variety of pro and anti-inflammatory cytokines, adipokines and cytokine-like angiogenic growth factors, production of which is altered in preeclampsia, driven (at least in part) by hypoxia. Altered levels of cytokines have been measured in the circulation of women with preeclampsia. While the placenta undoubtedly makes an important contribution to plasma cytokine levels, production by maternal peripheral blood mononuclear cells (PBMCs) and other tissues is also likely to be significant, although to what extent remains undetermined. Increased placental expression of soluble receptors occurs with preeclampsia, resulting in elevated circulating concentrations which confer impaired angiogenesis, deficient placental vascularisation, increased placental apoptosis and endothelial dysfunction. The extent to which these changes reflect a response to the disorder, as opposed to being a causative factor in the development of maternal disease is a matter of some debate. Nevertheless, convincing evidence is now accruing that autocrine/paracrine interactions between placental cytokines/growth factors and the maternal endothelium plays a central role in the pathogenesis of preeclampsia.

Corundum in Sulfide Ore at the Thompson Mine, Manitoba, Canada: An Unusual Occurrence of Cr- and Ni-Bearing Corundum

Abstract A novel type of corundum host environment is described from the Thompson Mine, northern Manitoba, where corundum occurs within a high-grade metamorphic reaction zone between boudinaged metaperidotite bodies, sulfide ore, and Al-rich pelitic schist of the Pipe Formation (Ospwagan Group). Zoned corundum porphyroblasts, up to 20 mm across, contain coevally formed sulfide inclusions, zircon, rutile, abundant exsolved rutile needles, and secondary sulfide inclusions formed within fractures. Retrograde alteration products of corundum include greenish muscovite (in contact with the schist) and diaspore (in contact with sulfides). The median concentrations of trace elements in Thompson corundum are as follows (in µg/g): 119 Mg, 1720 Ti, 69.9 V, 390 Cr, 8.2 Mn, 1924 Fe, 9.1 Ni, and 106 Ga. The geochemical signature of Thompson corundum (enrichment in Fe, Cr, and Ni) resembles that of ruby in other metamorphic and metasomatic mafic-ultramafic-hosted deposits, and the Cr concentration is comparable to the low range of rubies. Thompson corundum contains high Ni concentrations relative to most Cr-enriched corundum occurrences, a result of formation in an exceptionally Ni-rich environment. The high abundance of exsolved rutile inclusions imparts a dominantly brownish-gray color to the corundum, which precludes it from being of gem quality. Chromium-bearing corundum has been suggested as a possible indicator mineral for metamorphosed massive sulfide deposits, however, it is an indirect indicator that risks yielding false positives. Further investigation into Ni concentrations in corundum, a potential indicator of formation in a Ni-rich environment, is recommended.

Frictional Stability of Laumontite Under Hydrothermal Conditions and Implications for Injection‐Induced Seismicity in the Gonghe Geothermal Reservoir, Northwest China

AbstractLaumontite is a common and potentially frictionally unstable hydrothermal alteration product present in deep faults of the Gonghe EGS reservoir. We characterize the friction‐stability characteristics of synthetic laumontite gouge under in situ reservoir conditions. The pure laumontite gouge is frictionally strong (μ = 0.73–0.98) and the quartz/laumontite mixture (1:1) is generally less strong (μ = 0.73–0.78) under experimental conditions (Pc = 95 MPa, T = 90–250°C, Pf = 0–90 MPa). The shear velocity was stepped between 6.1, 0.61, then 0.061 μm/s for our experiments. For both gouges, the friction coefficient is independent of temperature and increases with elevated pore pressures. The pure gouge and mixture are strongly velocity‐weakening over a broad range in temperatures (∼90–220°C) and excess pore pressures (0–90 MPa) relevant to the Gonghe stimulation. Microearthquakes (MEQs) observed during stimulation are confined to within the broad depth range of inferred frictional instability—although fluid overpressures are also limited to this region. The observation that laumontite mixtures are frictionally unstable over a broad range of pressures and especially temperatures representative of EGS reservoirs and insensitive to the presence of the coexisting mineral phase (quartz) suggests its presence is a strong indicator of potential seismic hazard.

Hydrothermal alteration of accessory minerals (allanite and titanite) in the late Archean Closepet granitoid (Dharwar Craton, India): A TEM study

Allanite, a member of the epidote supergroup, is a widespread rare earth element (REE)-rich accessory mineral in the late Archean Closepet batholith (Dharwar craton, India). It is commonly associated with titanite. Previously recognized shear zones served as preferential paths for magma and later fluids. As a response to hydrothermal activity, allanite exhibits complex alteration textures, geochemical features, and breakdown products that vary across the batholith. In the central zone, allanite displays the largest variations. It has decomposed into secondary allanite, bastnäsite, chlorite, thorite, calcite, pyrite, and galena. In the southern zone, magmatic allanite core is preserved. The alteration products in the marginal regions are limited to secondary allanite, bastnäsite, chlorite, thorite, and synchysite. The breakdown products and textural features of allanite in the northern intrusions differ strongly from those in the other zones of the Closepet batholith and are limited to secondary allanite and chamosite. However, nanoscale element remobilization at the interface between allanite and titanite is evident. The observed texture in allanite indicates a complete dissolution–reprecipitation process. The chemical variations and differences in alteration products after allanite indicate that the fluid composition changed along the Closepet granitoid. The fluids that altered the allanite were most likely F-, Cl-, and CO2-rich and alkaline but eventually became acidic. When the chlorine-bearing fluids reached the northern zone, the concentrations or active contributions of CO2, F and H2S were very low. The alteration products (bastnäsite, chlorite, and thorite) indicate a rather low-temperature fluid.

A comprehensive study of apatite grains in Ryugu rock fragments

AbstractApatite is present as an accessory phase in many meteorites and is often formed as a secondary product of aqueous alteration. Its propensity to incorporate rare earth elements (REE) results in apatite usually being the main REE‐bearing phase in hydrously altered meteorites. Asteroid Ryugu is thought to have experienced pervasive aqueous alteration and material collected from the surface of Ryugu is expected to provide insight into asteroidal aqueous alteration processes without influence by terrestrial weathering. Morphologies and mineral associations of apatite grains from five rock fragments collected from the asteroid Ryugu by the Hayabusa2 spacecraft were examined and their REE concentrations were measured by synchrotron X‐ray fluorescence (SXRF) spectroscopy. The main minerals associated with apatite are dolomite, magnetite, and pyrrhotite. Grain boundary corrosion of the interfaces between apatite assemblages and the surrounding matrix suggest that paragenetic formation on the asteroid was followed by a later episode of hydrous alteration. Light REE (LREE) concentration levels recorded at 20–150 times those of bulk CI levels together with a steady increase from LREE toward enrichment of medium REE (MREE, up to Er) at 50–400 times bulk CI levels may suggest postgenetic removal of LREE from Ryugu apatite grains by late‐stage circulation of a hydrothermal fluid.

Are Clay Minerals Systematically the Products of Aqueous Alteration in Cosmic Bodies?

The formation of chondrite materials represents one of the earliest mineralogical processes in the solar system. Phyllosilicates are encountered at various stages of the chondrule formation, from the initial stages (IDP agglomerates) to the final steps (chondrule internal alteration). While typically linked to aqueous alteration, recent studies reveal that phyllosilicates could precipitate directly from residual fluids in post-magmatic or deuteric conditions and under a wide range of temperatures, pressures, water/rock ratios, and H2/H2O ratio conditions. This study re-examined the formation of hydrated phyllosilicates in chondrules and associated fine-grained rims (FGRs) using published petrographical, mineralogical, and chemical data on carbonaceous chondrites. Given that chondrules originate from the melting of interplanetary dust particles, the water liberated by the devolatilization of primary phyllosilicates, including clay minerals or ice melting, reduces the melting temperature and leads to water dissolution into the silicate melt. Anhydrous minerals (e.g., olivine and diopside) form first, while volatile and incompatible components are concentrated in the residual liquid, diffusing into the matrix and forming less porous FGRs. Serpentine and cronstedtite are the products of thermal metamorphic-like mineral reactions. The mesostasis in some lobated chondrules is composed of anhydrous and hydrous minerals, i.e., diopside and serpentine. The latter is probably not the alteration product of a glassy precursor but rather a symplectite component (concomitant crystallization of diopside and serpentine). If so, the symplectite has been formed at the end of the cooling process (eutectic-like petrographical features). Water trapped inside chondrule porosity can lead to the local replacement of olivine by serpentine without external water input (auto-alteration). In the absence of water, hydrated phyllosilicates do not crystallize, forming a different mineral assemblage.

Unveiling the altered metabolic pathways induced by nivolumab in non-small cell lung cancer via GC–MS metabolomics approach coupled with multivariate analysis

This research investigates the effects of the immunotherapeutic agent nivolumab on the metabolism of lung cancer cells (NCI-H1975) using GC–MS metabolomic profiling. Multivariate analysis such as unsupervised PCA and supervised OPLS-DA along with univariate analysis and pathway analysis were employed to explore the metabolomic data and identify altered metabolic pathways induced by nivolumab treatment. The study revealed distinct metabolic alterations in cancer cells, linked to proliferative and survival advantages, such as enhanced glycolysis, increased glutaminolysis, and modified amino acid metabolism. Key findings indicate elevated levels of glycolysis-related metabolites (glycine, alanine, pyruvate, and lactate) and TCA cycle intermediates (succinate, fumarate, malate) in cancer cells, with a significant decrease following nivolumab treatment. Additionally, lower levels of aspartic acid and citrate in cancer cells imply altered nucleotide synthesis and fatty acid production essential for tumor growth. Treatment with nivolumab also reduced oleic acid levels, indicative of its effect on disrupted lipid metabolism. Our research shows nivolumab's potential to modify metabolic pathways involved in lung cancer progression, suggesting its dual role in cancer therapy: as an immune response modulator and a metabolic pathway disruptor.

Analysis of News Source Selection in the Digital Age: A Case Study of Micro-platforms Operated by People’s Daily and Southern Weekly

This study employs content analysis to compare and examine the selection of news sources in the micro-platforms of mainstream media, People’s Daily, and urban media, Southern Weekly. It attempts to interpret the impact of the digitalization process on the content production practices of different news media in China. The research reveals that in the digital era, media attributes and platform regulations are direct factors influencing the selection of news sources in news production. This transformation has significantly altered traditional news content production. Official news sources remain the primary choice for news media in producing content in the digital age. Additionally, grassroots news sources, representing the general public, are gradually incorporated into various types of reporting, demonstrating a trend towards democratization.

Soils on Recent Tephra of the Somma–Vesuvius Volcanic Complex, Italy

The Somma–Vesuvius volcanic complex emitted huge quantities of volcanic materials over a period from before 18,300 years BP to 1944. The activity during the last period, from post-AD 1631 to 1944, primarily produced lava and pyroclastics via effusive and strombolian eruptions. We investigated the pedogenesis on rocks formed from post-AD 1631 to 1944, occurring on the slopes of Mt. Vesuvius up to Gran Cono Vesuviano and in the northern valley separating Vesuvius from the older Mt. Somma edifice. Pertinent morphological, physical, chemical, and mineralogical (XRD and FT-IR) soil properties were studied. The results indicated the existence of thin and deep stratified soils on lava, as well as the presence of loose detritic covers formed via pyroclastic emplacement and redistribution. The soils showed minimal profile differentiation, frequently with layering recording the episodic addition of sediments. We found that the dominant coarse size of primary mineral particles was preserved, and there was a low level of clay production. The main mineralogical assemblage present in sands also persisted in clays, indicating the physical breaking of the parent material. Chemical weathering produced mineral modifications towards the active forms of Al and Fe and was also attested in selected soils by glass alteration, allophane production, and the presence of analcime in clay as a secondary product from leucite. The differences in glass alteration and analcime production found in the selected soils on lava were related to soil particle size and soil thickness. Concerning the youngest soil present on Gran Cono Vesuviano, other factors, such as the substratum’s age and site elevation, appeared to be implicated.

Chronic dietary exposure to a glyphosate-based herbicide alters ovarian functions in young female broilers

Glyphosate (GLY)-based herbicide (GBH) formulations are widely used pesticides in agriculture. The European Union recently decided to extend the use of GLY in Europe until 2034. Previously, we showed that chronic dietary GBH exposure in adult hens resulted in a reversible increase in early mortality in chicken embryos. In this present study, we investigated the GBH effects on metabolism and ovarian functions by using a transcriptomic approach in vivo in young female broilers and in vitro in ovarian explant cultures. We exposed 11-day-old female broilers to 13 mg GLY equivalent/kg body weight/day (GBH13, n = 20), 34 mg GLY equivalent/kg body weight/day (GBH34, n = 20), or a standard diet (control [CT], n = 20) for 25 days. These two GBH concentrations correspond to approximatively one eighth and one third of the no observed adverse effect level (NOAEL) as defined by European Food Safety Authority in birds. During this period, we evaluated body weight, fattening, food intake, and the weight of organs (including the ovaries). Chronic dietary GBH exposure dose dependently reduced food intake, body weight, and fattening, but increased oxidative stress and relative ovary weight. We analyzed the ovarian gene expression profile in CT, GBH13, and GBH34 broilers with RNA sequencing and showed that differentially expressed genes are mainly enriched in pathways related to cholesterol metabolism, steroidogenesis, and RNA processing. With quantitative polymerase chain reaction and western blotting, we confirmed that GBH decreased ovarian STAR and CYP19A1 messenger RNA and protein expression, respectively. Furthermore, we confirmed that GBH altered steroid production in ovarian explants. We have identified potential regulatory networks associated with GBH. These data provide valuable support for understanding the ovarian transcriptional regulatory mechanism of GBH in growing broilers.

Ermeloite, AlPO4⋅H2O a new phosphate mineral with kieserite-type structure from Galicia, Spain

AbstractErmeloite is a new aluminium phosphate mineral from Galicia, Spain, in the northwest of the Iberian Peninsula. It is the third formally recognised mineral discovered in Galicia since morenosite and cervantite in the 19th Century. The name and symbol (Erm) were approved by the Commission on New Minerals, Nomenclature and Classification of the International Mineralogical Association (IMA2021–017a) in recognition of the geographical location where it was found. The mineral occurs as a light blue to white fine aggregate over quartz and microcline associated with wardite. Crystals of ~0.04 mm are transparent and have a waxy lustre. The simplified empirical formula determined using electron microprobe analysis is Al1.02P0.95F0.06O3.88⋅1.06 H2O, which is near to the ideal formula Al(PO4)⋅H2O. The mineral is an alteration product within a phosphate pegmatite. Ermeloite is the second phosphate isostructural with the sulfates of the kieserite group. Single-crystal X-ray diffraction showed that ermeloite crystallises in the monoclinic C2/c space group with cell parameters a = 6.5371(4) Å, b = 7.5670(5) Å, c = 7.1146(5) Å, β = 115.335(2)°, V = 318.08(4) Å3 and Z = 4 at room temperature. Comparative analysis of the crystallographic data, with isostructural phosphates, revealed an interesting behaviour for these compounds.

Effects of alimentary-derived bacterial metabolites on energy metabolism in colonic epithelial cells and inflammatory bowel diseases

In this review, we present the main luminal fuels that are responsible for energy production in colonocytes, namely the bacterial metabolites short-chain fatty acids and lactate, which are produced from undigestible polysaccharides and proteins, and hydrogen sulfide that is mainly produced from undigested proteins. In addition to these luminal fuels, colonocytes can use glutamine, and to a lower extent glucose, as energy substrates provided by arterial capillaries. The effects of excessive concentrations of bacterial metabolites within the colonic luminal fluid (including butyrate, hydrogen sulfide, p-cresol, indole derivatives, ammonia, 4-hydroxyphenylacetic acid, and acetaldehyde) on the mitochondrial energy metabolism in colonic epithelial cells and the consequences of altered ATP production on the colonic epithelium renewal and barrier function are detailed, as well as consequences for water and electrolyte absorption. The relationships between modifications of these latter processes and development of colitis are then discussed. Finally, several mechanisms that are considered as adaptive against deleterious effects of bacterial metabolites on colonic epithelial cell energy metabolism are presented.

A review of the role of testosterone in the care of the critically ill patient.

Testosterone is an anabolic and androgenic steroid hormone therapeutically used to produce male sex characteristics. It has also been shown to have a modulating effect on proinflammatory biomarkers. Critical illness is characterised by a proinflammatory and catabolic state and is accompanied by altered testosterone production, which may persist into the recovery phase. Testosterone may, therefore be a potential therapeutic option in critical illness. This paper reviews normal testosterone physiology, and the changes seen during critical illness and systematically reviews testosterone therapy during both the acute and chronic phases of critical illness. This article explains the pathophysiology of testosterone during critical illness and explores the therapeutic value of testosterone in the management of critically ill patients.

Insulin-like growth factor-1 promotes the testicular sperm production by improving germ cell survival and proliferation in high-fat diet-treated male mice.

A decrease in semen volume among men is comparable to the rising prevalence of obesity worldwide. The anabolic hormone insulin-like growth factor-1 (IGF-1) can promote proliferation and differentiation in cultured mouse spermatogonial stem cells and alleviate abnormal in vitro spermatogenesis. Additionally, serum IGF-1 level is negatively correlated with body mass index. Whereas the role of IGF-1 in the sperm production in obese men remains unclear. To investigate the therapeutic effect and potential mechanism of IGF-1 on spermatogenesis of high-fat diet (HFD)-induced obesity mice. An HFD-induced obesity mouse model was established. Alterations in testicular morphology, sperm count, proliferation, and apoptosis were observed by H&E staining,immunohistochemistry, immunofluorescence, and Western blotting. Exogenous recombinant IGF-1 was administered to obese mice to investigate the correlations between altered testicular IGF-1 levels and sperm production. The sperm count was reduced, the testicular structure was disordered, and sex hormone levels were abnormal in HFD-fed mice compared with normal diet-fed mice. The expression of proliferation-related antigens such as proliferating cell nuclear antigen (PCNA) and Ki-67 was decreased, while that of proapoptotic proteins such as c-caspase3 was increased in testes from HFD-fed mice. Most importantly, the phosphorylation of insulin-like growth factor-1 receptor (IGF-1R) in testes was decreased due to reductions in IGF-1 from hepatocytes and Sertoli cells. Recombinant IGF-1 alleviated these functional impairments by promoting IGF-1R, Akt, and Erk1/2 phosphorylation in the testes. Insufficient IGF-1/IGF-1R signaling is intimately linked to damaged sperm production in obese male mice. Exogenous IGF-1 can improve survival and proliferation as well as sperm production. This study provides a novel theoretical basis and a target for the treatment of obese men with oligozoospermia.

Lower malathion concentrations reduce testosterone biosynthesis by Leydig TM3 cells in vitro by altering cellular redox profile and inducing oxidative damage

Malathion is an organophosphate pesticide used in agriculture and control of the Aedes aegypti mosquito. As previous reports have indicated the potential of malathion to compromise testosterone production in in vivo models, the objective of this study was to elucidate the mechanisms underlying the impairment of Leydig cell function, considering its critical role in male reproductive function. To this end, murine Leydig TM3 cells were exposed to concentrations of 1, 10, 100 or 1000 μM malathion for 24 h for evaluation of the compound on cell viability. Subsequently, concentrations of 1, 10, and 100 μM malathion were employed for a 24-h period to assess testosterone biosynthesis, levels of cytokines IL-1β, IL-6, IL-10, and TNF-α, as well as the redox profile. Malathion exerted a concentration-dependent impact on cell viability. Notably, the lower concentrations of malathion (1 and 10 μM) were found to impair testosterone biosynthesis in TM3 cells. While there were changes in IL-1 and TNF-α levels at specific concentrations, no direct correlation with altered hormone production was established. Our investigation revealed that varied malathion concentrations induced oxidative stress by increase in superoxide anion and a compensatory rise in antioxidants. In conclusion, the observed changes in the oxidative profile of TM3 cells were linked to functional impairment, evidenced by reduced testosterone biosynthesis at lower malathion concentrations.

Cytoprotective mechanism of cerebro-cognitive reserve

IntroductionConsideration of the reserve problem would be incomplete without an analysis of the cytoprotective mechanism. The predominant molecular hallmark of aging and degeneration is the accumulation of altered gene products. Moreover, several conditions, including protein, lipid, or glucose oxidation, disrupt redox homeostasis and lead to the accumulation of unfolded or misfolded proteins in the aging brain in case of AD, and other neurodegenerative diseases that have as a common denominator abnormal protein production, mitochondrial dysfunction and oxidative stress. Some authors classify aging, pathological aging, and neurodegeneration as “protein conformational diseases”.Objectivesscientific publicationsMethodsanalytical reviewResults The central nervous system has evolved a conserved unfolded protein response mechanism to cope with the accumulation of misfolded proteins. As one of the main intracellular redox systems involved in neuroprotection, the vitagene system becomes a potential neurohormetic target for novel cytoprotective interventions. Vitagens encode the cytoprotective heat shock proteins (Hsp) Hsp70 and heme oxygenase-1, as well as thioredoxin reductase and sirtuins. The cellular stress response is the ability of a cell to withstand stressful conditions, including the heat shock response. The production of heat shock proteins, including protein chaperones, is necessary for the folding and repair of damaged proteins, which promotes cell survival to avoid apoptosis.«Molecular chaperone» are proteins that function as part of an ancient defense system in our cells. They promote cell survival by sequestering damaged proteins and preventing their aggregation. Chaperone complexes are involved in the regulation of mitochondrial functions, assembly of the cytoplasmic proteolytic system of brain cells. The cellular response to stress requires the activation of survival pathways that are under the control of protective genes called vitagens. Vitagens are involved in the production of heat-shock protein molecules, glutathione, and bilirubin. They have antioxidant and anti-apoptotic activity and provide protection against oxidative stress.Conclusions Studies have shown that the heat shock response contributes to the maintenance of cellular homeostasis, the establishment of a cytoprotective state in a wide range of human diseases, including inflammation, cancer, aging, and neurodegenerative disorders. Endogenous proteins can be manipulated by food or pharmacological compounds, which represents an innovative approach to therapeutic intervention in neurodegenerative disorders, actually influencing reserve mechanisms and adaptive capacity.Disclosure of InterestNone Declared

Anaerobic fungi in the tortoise alimentary tract illuminate early stages of host-fungal symbiosis and Neocallimastigomycota evolution

Anaerobic gut fungi (AGF, Neocallimastigomycota) reside in the alimentary tract of herbivores. While their presence in mammals is well documented, evidence for their occurrence in non-mammalian hosts is currently sparse. Culture-independent surveys of AGF in tortoises identified a unique community, with three novel deep-branching genera representing >90% of sequences in most samples. Representatives of all genera were successfully isolated under strict anaerobic conditions. Transcriptomics-enabled phylogenomic and molecular dating analyses indicated an ancient, deep-branching position in the AGF tree for these genera, with an evolutionary divergence time estimate of 104-112 million years ago (Mya). Such estimates push the establishment of animal-Neocallimastigomycota symbiosis from the late to the early Cretaceous. Further, tortoise-associated isolates (T-AGF) exhibited limited capacity for plant polysaccharides metabolism and lacked genes encoding several carbohydrate-active enzyme (CAZyme) families. Finally, we demonstrate that the observed curtailed degradation capacities and reduced CAZyme repertoire is driven by the paucity of horizontal gene transfer (HGT) in T-AGF genomes, compared to their mammalian counterparts. This reduced capacity was reflected in an altered cellulosomal production capacity in T-AGF. Our findings provide insights into the phylogenetic diversity, ecological distribution, evolutionary history, evolution of fungal-host nutritional symbiosis, and dynamics of genes acquisition in Neocallimastigomycota.

Abstract 3980: Investigating the role of host obesity in promoting immunotherapy resistance

Abstract Obesity is linked to an increased risk of various cancers, including renal cell carcinoma (RCC). Many RCC patients have obesity at diagnosis and treatment initiation, and our lab has found that this significantly impairs immunotherapy outcomes. Both preclinical and clinical reports, from our lab and others, have demonstrated that obesity reduces the efficacy of CD8+ T cell-dependent immunotherapy by increasing pro-tumorigenic IL-1β. Combining anti-PD-1 based therapy with anti-IL-1β triggers the recruitment of CD8+ T cells and improves the efficacy of anti-PD-1 based immunotherapy. However, the mechanistic links between obesity and increased IL-1β production remains unknown. Our objective is to identify mechanisms promoting IL-1 β-driven immunosuppression within renal tumors of obese mice. In our in vivo studies, we utilized a BALB/c mouse model of diet-induced obesity (DIO) and lean controls in combination with the Renca-Luc RCC cell line. Using flow cytometry and western blot, we respectively assessed leukocyte populations producing IL-1β and tumor energetics. Flow cytometry revealed that intra-tumoral IL-1β is produced primarily by tumor associated macrophages (TAMS). Immunoblotting demonstrated that increased IL-1β production is linked to altered mitochondrial function and ATP production. These early findings support the hypothesis that obesity driven IL-1β expression is mediated by tumor-associated macrophages and that mitochondrial dysfunction drives immune suppression. Understanding these molecular and immune-related mechanisms may pave the way for novel strategies to reduce immunosuppression in obese RCC patients, thus improving immunotherapeutic efficacy and overall clinical outcomes. Citation Format: Henry Nnaemeka Ogbonna, Zachary Roberts, Haley Kvarnberg, Francesca Dempsey, Patrick N. Song, Anna G. Sorace, Lyse Norian. Investigating the role of host obesity in promoting immunotherapy resistance [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 3980.

Abstract P536: The Association of Adipokines With Cardiac Structure and Function Among Older Adults Without Clinical Cardiovascular Disease

Background: Heart failure (HF) is a growing public health concern. While dysfunctional adipose tissue is a key driver of HF risk in the population, the role of altered adipokine production by adipose tissue in the development of cardiac dysfunction is unknown. Methods: We conducted a cross-sectional analysis of ARIC Visit 5 (2011-13) participants free of coronary heart disease and HF. Using linear regression, we assessed the adjusted associations between the adipokines adiponectin, leptin, apelin, and resistin (per 1-SD) and echocardiographic parameters indicative of cardiac structure and function. Results: We included 3244 participants (mean age 75±5 years, 61% female, 16% Black, 31% with obesity). After adjusting for sociodemographic/lifestyle factors and eGFR, 1-SD higher adiponectin was associated with lower (worse) LV ejection fraction (LVEF), but a more negative (better) longitudinal strain (LS). Higher adiponectin was also associated with higher lateral and medial e’ and lower E/e’, reflecting better diastolic function. Conversely, higher leptin was associated with worse systolic and diastolic function, indicated by a less negative LS, lower lateral and medial e’, and higher E/e’. Higher leptin/adiponectin ratio was associated with better LVEF (β: 1.73, 95% CI: 0.04, 3.41), but worse LS (β: 1.87, 95% CI: 1.17, 2.57), as well as uniformly worse diastolic function (lateral e’ [β: -2.39, 95% CI: -2.99, -1.79], medial e’ [β: -1.43, 95% CI: -1.86, -0.99], E/e’ [β: 2.61, 95% CI: 1.56, 3.67]). Adjustment for clinical variables and BMI attenuated some associations, but resulted in associations of adiponectin with greater LV mass index, and leptin with lower LV mass index. Apelin and resistin had weak associations with cardiac function. Conclusion: Adiponectin and leptin are differentially associated with systolic and diastolic function. Further investigation of the adipokines’ opposing roles in the development of cardiac dysfunction may help elucidate the effect of dysfunctional adipose tissue on myocardium.