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19 pages, 1050 KiB  
Article
Fungal Communities in Soils Contaminated with Persistent Organic Pollutants: Adaptation and Potential for Mycoremediation
by Lazaro Alexis Pedroso Guzman, Lukáš Mach, Jiřina Marešová, Jan Wipler, Petr Doležal, Jiřina Száková and Pavel Tlustoš
Appl. Sci. 2025, 15(15), 8607; https://doi.org/10.3390/app15158607 (registering DOI) - 4 Aug 2025
Viewed by 101
Abstract
The main objective of this study was to select indigenous fungal species suitable for the potential mycoremediation of the soils polluted by organic pollutants. As a sampling area, Litvínov City (North Bohemia, Czech Republic) was selected. The city is characterized by intensive coal [...] Read more.
The main objective of this study was to select indigenous fungal species suitable for the potential mycoremediation of the soils polluted by organic pollutants. As a sampling area, Litvínov City (North Bohemia, Czech Republic) was selected. The city is characterized by intensive coal mining, coal processing, and the chemical industry, predominantly petrochemistry. The elevated contents of persistent organic pollutants (POPs) such as polyaromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were identified in urban soils due to the long-term industrial pollution. The results confirmed elevated contents of PAHs in all the analyzed soil samples with high variability ranging between 0.5 and 23.3 mg/kg regardless of the position of the sampling area on the city map. PCBs and PCDD/Fs exceeded the detection limits in the soil at the sampling points, and several hotspots were revealed at some locations. All the sampling points contained a diverse community of saprotrophic and mycorrhizal fungi, as determined according to abundant basidiomycetes. Fungal species with a confirmed ability to degrade organic pollutants were found, such as species representing the genera Agaricus from the Agaricaceae family, Coprinopsis from the Psathyrellaceae family, Hymenogaster from the Hymenogasteraceae family, and Pluteus from the Pluteaceae family. These species are accustomed to particular soil conditions as well as the elevated contents of the POPs in them. Therefore, these species could be taken into account when developing potential bioremediation measures to apply in the most polluted areas, and their biodegradation ability should be elucidated in further research. The results of this study contribute to the investigation of the potential use of fungal species for mycoremediation of the areas polluted by a wide spectrum of organic pollutants. Full article
(This article belongs to the Section Ecology Science and Engineering)
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13 pages, 2414 KiB  
Article
In Silico Characterization of Molecular Interactions of Aviation-Derived Pollutants with Human Proteins: Implications for Occupational and Public Health
by Chitra Narayanan and Yevgen Nazarenko
Atmosphere 2025, 16(8), 919; https://doi.org/10.3390/atmos16080919 - 29 Jul 2025
Viewed by 281
Abstract
Combustion of aviation jet fuel emits a complex mixture of pollutants linked to adverse health outcomes among airport personnel and nearby communities. While epidemiological studies showed the detrimental effects of aviation-derived air pollutants on human health, the molecular mechanisms of the interactions of [...] Read more.
Combustion of aviation jet fuel emits a complex mixture of pollutants linked to adverse health outcomes among airport personnel and nearby communities. While epidemiological studies showed the detrimental effects of aviation-derived air pollutants on human health, the molecular mechanisms of the interactions of these pollutants with cellular biomolecules like proteins that drive the adverse health effects remain poorly understood. In this study, we performed molecular docking simulations of 272 pollutant–protein complexes using AutoDock Vina 1.2.7 to characterize the binding strength of the pollutants with the selected proteins. We selected 34 aviation-derived pollutants that constitute three chemical categories of pollutants: volatile organic compounds (VOCs), polyaromatic hydrocarbons (PAHs), and organophosphate esters (OPEs). Each pollutant was docked to eight proteins that play critical roles in endocrine, metabolic, transport, and neurophysiological functions, where functional disruption is implicated in disease. The effect of binding of multiple pollutants was analyzed. Our results indicate that aliphatic and monoaromatic VOCs display low (<6 kcal/mol) binding affinities while PAHs and organophosphate esters exhibit strong (>7 kcal/mol) binding affinities. Furthermore, the binding strength of PAHs exhibits a positive correlation with the increasing number of aromatic rings in the pollutants, ranging from nearly 7 kcal/mol for two aromatic rings to more than 15 kcal/mol for five aromatic rings. Analysis of intermolecular interactions showed that these interactions are predominantly stabilized by hydrophobic, pi-stacking, and hydrogen bonding interactions. Simultaneous docking of multiple pollutants revealed the increased binding strength of the resulting complexes, highlighting the detrimental effect of exposure to pollutant mixtures found in ambient air near airports. We provide a priority list of pollutants that regulatory authorities can use to further develop targeted mitigation strategies to protect the vulnerable personnel and communities near airports. Full article
(This article belongs to the Section Air Quality and Health)
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20 pages, 2063 KiB  
Article
Chemometric Evaluation of 16 Priority PAHs in Soil and Roots of Syringa vulgaris and Ficus carica from the Bor Region (Serbia): An Insight into the Natural Plant Potential for Soil Phytomonitoring and Phytoremediation
by Aleksandra D. Papludis, Slađana Č. Alagić, Snežana M. Milić, Jelena S. Nikolić, Snežana Č. Jevtović, Vesna P. Stankov Jovanović and Gordana S. Stojanović
Environments 2025, 12(8), 256; https://doi.org/10.3390/environments12080256 - 28 Jul 2025
Viewed by 309
Abstract
The soil phytomonitoring and phytostabilization potential of Syringa vulgaris and Ficus carica was evaluated regarding 16 priority polycyclic aromatic hydrocarbons (PAHs) using a chemometric approach and the calculation of bioconcentration factors (BCFs) for each individual PAH in plants’ roots from each selected location [...] Read more.
The soil phytomonitoring and phytostabilization potential of Syringa vulgaris and Ficus carica was evaluated regarding 16 priority polycyclic aromatic hydrocarbons (PAHs) using a chemometric approach and the calculation of bioconcentration factors (BCFs) for each individual PAH in plants’ roots from each selected location in the Bor region. PAHs in roots and the corresponding soils were analyzed using the QuEChERS (Quick, Effective, Cheap, Easy, Rugged, Safe) method with some new modifications, gas chromatography/mass spectrometry, Pearson’s correlation study, hierarchical cluster analysis, and BCFs. Several central conclusions are as follows: Each plant species developed its own specific capability for PAH management, and root concentrations ranged from not detected (for several compounds) to 5592 μg/kg (for fluorene in S. vulgaris). In some cases, especially regarding benzo(a)pyrene and chrysene, both plants had a similar tactic—the total avoidance of assimilation (probably due to their high toxicity). Both plants retained significant quantities of different PAHs in their roots (many calculated BCFs were higher than 1 or were even extremely high), which recommends them for PAH phytostabilization (especially fluorene, benzo(b)fluoranthene, and benzo(k)fluoranthene). In soil monitoring, neither of the plants are helpful because their roots do not reflect the actual situation found in soil. Finally, the analysis of the corresponding soils provided useful monitoring information. Full article
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19 pages, 1186 KiB  
Article
The Genotoxic Potential of Organic Emissions from Domestic Boilers Combusting Biomass and Fossil Fuels
by Jitka Sikorova, Frantisek Hopan, Lenka Kubonova, Jiri Horak, Alena Milcova, Pavel Rossner, Antonin Ambroz, Kamil Krpec, Oleksandr Molchanov and Tana Zavodna
Toxics 2025, 13(8), 619; https://doi.org/10.3390/toxics13080619 - 25 Jul 2025
Viewed by 180
Abstract
Solid fuels are still widely used in household heating in Europe and North America. Emissions from boilers are released in proximity to people. Therefore, there is a need to minimise the toxicity of emissions affecting human health to the greatest extent possible. This [...] Read more.
Solid fuels are still widely used in household heating in Europe and North America. Emissions from boilers are released in proximity to people. Therefore, there is a need to minimise the toxicity of emissions affecting human health to the greatest extent possible. This study compares the genotoxic potential of the emissions of four boilers of modern and old design (automatic, gasification, down-draft, over-fire) operating at reduced output to simulate the real-life combustion fed by various fossil and renewable solid fuels (hard coal, brown coal, brown coal briquettes, wood pellets, wet and dry spruce). Organic emissions were tested for genotoxic potential by analysing bulky DNA adducts and 8-oxo-dG adduct induction. There was no consistent genotoxic pattern among the fuels used within the boilers. Genotoxicity was strongly correlated with polycyclic aromatic hydrocarbon (PAH) content, and even stronger correlation was observed with particulate matter (PM). In all measured variables (PM, PAHs, genotoxicity), the technology of the boilers was a more important factor in determining the genotoxic potential than the fuels burned. The highest levels of both bulky and 8-oxo-dG DNA adducts were induced by organics originating from the over-fire boiler, while the automatic boiler exhibited genotoxic potential that was ~1000- and 100-fold lower, respectively. Full article
(This article belongs to the Section Human Toxicology and Epidemiology)
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15 pages, 1406 KiB  
Article
Arterial Stiffness and Early Cardiac Dysfunction in Type 2 Diabetes Mellitus: A Potential Role for 25 OH Vitamin D3 Deficiency
by Laura Maria Craciun, Florina Buleu, Stela Iurciuc, Daian Ionel Popa, Gheorghe Nicusor Pop, Flavia Goanta, Greta-Ionela Goje, Ana Maria Pah, Marius Badalica-Petrescu, Olivia Bodea, Ioana Cotet, Claudiu Avram, Diana-Maria Mateescu and Adina Avram
Medicina 2025, 61(8), 1349; https://doi.org/10.3390/medicina61081349 - 25 Jul 2025
Viewed by 157
Abstract
Background and Objectives: Type 2 diabetes mellitus (T2DM) is associated with subclinical cardiovascular changes, such as increased arterial stiffness and myocardial dysfunction. Vitamin D deficiency has been recognized as a potential contributing factor to vascular disease; however, its impact on early cardiac [...] Read more.
Background and Objectives: Type 2 diabetes mellitus (T2DM) is associated with subclinical cardiovascular changes, such as increased arterial stiffness and myocardial dysfunction. Vitamin D deficiency has been recognized as a potential contributing factor to vascular disease; however, its impact on early cardiac changes associated with T2DM remains poorly understood. Our aim was to evaluate the association between serum levels of 25-hydroxyvitamin D3 [25(OH)D3], arterial stiffness, and left ventricular global longitudinal strain (LV GLS) in patients with T2DM who do not have a clinically evident cardiovascular disease. Material and methods: This cross-sectional study evaluated the carotid intima–media thickness (IMT), aortic pulse wave velocity (PWVao), LV GLS, and serum 25(OH)D3 levels in patients diagnosed with T2DM (n = 65) compared to healthy control subjects (n = 55). Independent predictors of arterial stiffness were identified by a multivariate logistic regression analysis. Results: Patients with T2DM showed a significant increase in IMT and PWVao, a reduction in LV GLS, and low levels of 25(OH)D3 compared to subjects in the control group (all p < 0.05). Both vitamin D deficiency and T2DM were found to be independently associated with an increased arterial stiffness, with odds ratios of 2.4 and 4.8, respectively. A significant inverse relationship was identified between 25(OH)D3 levels and markers of arterial stiffness, as well as LV GLS, suggesting a possible association between the vitamin D status and the early onset of cardiovascular dysfunction. Conclusions: Patients with T2DM show early signs of heart and blood vessel problems, even with an ejection fraction that remains within normal limits. There is a significant correlation between vitamin D deficiency and increased arterial stiffness, along with impaired LV GLS, indicating its possible involvement in cardiovascular complications associated with diabetes. These findings support the utility of integrating vascular, myocardial, and vitamin D assessments in early cardiovascular risk stratification for T2DM patients. Full article
(This article belongs to the Special Issue Cardiovascular Diseases and Type 2 Diabetes: 2nd Edition)
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22 pages, 5657 KiB  
Article
SUL-150 Limits Vascular Remodeling and Ventricular Failure in Pulmonary Arterial Hypertension
by Lysanne M. Jorna, Dalibor Nakládal, Johannes N. van Heuveln, Diederik E. van der Feen, Quint A. J. Hagdorn, Guido P. L. Bossers, Annemieke van Oosten, Michel Weij, Ludmila Tkáčiková, Soňa Tkáčiková, Robert H. Henning, Martin C. Harmsen, Rolf M. F. Berger and Guido Krenning
Int. J. Mol. Sci. 2025, 26(15), 7181; https://doi.org/10.3390/ijms26157181 - 25 Jul 2025
Viewed by 261
Abstract
Pulmonary arterial hypertension (PAH) is a rare, progressive, and incurable disease characterized by an elevated pulmonary blood pressure, extensive remodeling of the pulmonary vasculature, increased pulmonary vascular resistance, and culminating in right ventricular failure. Mitochondrial dysfunction has a major role in the pathogenesis [...] Read more.
Pulmonary arterial hypertension (PAH) is a rare, progressive, and incurable disease characterized by an elevated pulmonary blood pressure, extensive remodeling of the pulmonary vasculature, increased pulmonary vascular resistance, and culminating in right ventricular failure. Mitochondrial dysfunction has a major role in the pathogenesis of PAH and secondary right ventricular failure, and its targeting may offer therapeutic benefit. In this study, we provide proof-of-concept for the use of the mitochondrially active drug SUL-150 to treat PAH. PAH was induced in rats by monocrotaline, followed by the placement of an aortocaval shunt one week later. The mitoprotective compound SUL-150 (~6 mg·kg−1·day−1) or vehicle was administered intraperitoneally via osmotic minipump for 28 days, implanted at the time of aortocaval shunt placement. Vehicle-treated PAH rats had dyspnea and showed pulmonary artery remodeling with increased responsiveness to phenylephrine, in addition to remodeling of the intrapulmonary arterioles. SUL-150 administration mitigated the dyspnea and the remodeling responses. Vehicle-treated PAH rats developed right ventricular hypertrophy, fibrosis, and failure. SUL-150 administration precluded cardiomyocyte hypertrophy and inhibited ventricular fibrogenesis. Right ventricular failure in vehicle-treated PAH rats induced mitochondrial loss and dysfunction associated with a decrease in mitophagy. SUL-150 was unable to prevent the mitochondrial loss but improved mitochondrial health in the right ventricle, which culminated in the preservation of right ventricular function. We conclude that SUL-150 improves PAH-associated morbidity by the amelioration of pulmonary vascular remodeling and right ventricular failure and may be considered a promising therapeutic candidate to slow disease progression in pulmonary arterial hypertension and secondary right ventricular failure. Full article
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12 pages, 1644 KiB  
Brief Report
RNA-Seq Identification of Peanut Callus-Specific Promoters and Evaluation of Base-Editing Efficiency
by Lulu Xue, Han Liu, Huanhuan Zhao, Pengyu Qu, Xiaona Li, Xiaobo Wang, Bingyan Huang, Ziqi Sun, Suoyi Han, Xiaodong Dai, Wenzhao Dong, Lei Shi and Xinyou Zhang
Plants 2025, 14(15), 2290; https://doi.org/10.3390/plants14152290 - 25 Jul 2025
Viewed by 265
Abstract
Prolonged expression of gene-editing components in CRISPR-modified plants can interfere with phenotypic analysis of target traits, increase the risk of off-target mutations, and lead to unnecessary metabolic burden. To mitigate these issues in peanut (Arachis hypogaea L.), callus-specific promoters were screened to [...] Read more.
Prolonged expression of gene-editing components in CRISPR-modified plants can interfere with phenotypic analysis of target traits, increase the risk of off-target mutations, and lead to unnecessary metabolic burden. To mitigate these issues in peanut (Arachis hypogaea L.), callus-specific promoters were screened to restrict Cas9 expression to the callus stage, minimizing its activity in regenerated plants. In this study, six callus-specific genes in peanut were identified by mining RNA sequencing datasets and validating their expression profiles using quantitative reverse transcriptase PCR. The promoters of Arahy.H0FE8D, Arahy.WT3AEF, Arahy.I20Q6X, Arahy.ELJ55T, and Arahy.N9CMH4 were cloned and assessed for their expression activity. Beta-glucuronidase (GUS) histochemical staining confirmed that all five promoters were functional in peanut callus. Further investigation revealed their ability to drive cytosine base editing via a deaminase-nCas9 fusion protein, with all promoters successfully inducing precise base substitutions in peanut. Notably, PAh-H0FE8D, PAh-WT3AEF, PAh-ELJ55T, and PAh-N9CMH4 exhibited comparable or higher editing efficiencies than the commonly used cauliflower mosaic virus 35S promoter. These findings provide valuable tools for improving the biosafety of CRISPR-based genome editing in peanut breeding programs. Full article
(This article belongs to the Special Issue Advances in Oil Regulation in Seeds and Vegetative Tissues)
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24 pages, 7845 KiB  
Article
Metabolomics and Lipidomics Explore Phenotype-Specific Molecular Signatures for Phenylketonuria
by Buket Yurteri Şahiner, Ali Dursun and Basri Gülbakan
Int. J. Mol. Sci. 2025, 26(15), 7171; https://doi.org/10.3390/ijms26157171 - 25 Jul 2025
Viewed by 313
Abstract
Phenylketonuria (PKU) is a monogenic disorder caused by pathogenic variants in the gene encoding phenylalanine hydroxylase (PAH), an enzyme essential for phenylalanine (Phe) metabolism. It is characterized by elevated Phe levels, leading to a wide spectrum of clinical phenotypes. These phenotypes are characterized [...] Read more.
Phenylketonuria (PKU) is a monogenic disorder caused by pathogenic variants in the gene encoding phenylalanine hydroxylase (PAH), an enzyme essential for phenylalanine (Phe) metabolism. It is characterized by elevated Phe levels, leading to a wide spectrum of clinical phenotypes. These phenotypes are characterized by varying Phe accumulation, dietary tolerance, and heterogeneous cognitive and neurological outcomes, but current monitoring methods, focused primarily on blood Phe levels, are limited in capturing this variability. In this study, we applied mass spectrometry-based advanced quantitative amino acid analyses, untargeted metabolomics, and lipidomics analyses. We examined the plasma metabolite and lipid profiles in a total of 73 individuals with various PKU phenotypes against healthy controls to see how the metabolome and lipidome of the patients change in different phenotypes. We investigated whether novel markers could be associated with metabolic control status. By elucidating the metabolic and lipid fingerprints of PKU’s phenotypic variability, our findings may provide novel insights that could inform the refinement of dietary and pharmacological interventions, thereby supporting the development of more personalized treatment strategies. Full article
(This article belongs to the Section Molecular Biology)
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14 pages, 728 KiB  
Article
Groundwater Quality Analysis: Assessing the Impact of a Closed Landfill—A Case Study on Physico-Chemical and Microplastic Contaminants
by Grzegorz Przydatek, Józef Ciuła, Narcis Barsan, Diana Mirila and Emilian Mosnegutu
Appl. Sci. 2025, 15(15), 8223; https://doi.org/10.3390/app15158223 - 24 Jul 2025
Viewed by 308
Abstract
In the context of increasing concern over long-term environmental impacts of closed landfill sites, this study investigates the composition of groundwater and leachate at a municipal waste landfill in southwestern Poland, two decades after its closure. The research, conducted in 2023, aimed to [...] Read more.
In the context of increasing concern over long-term environmental impacts of closed landfill sites, this study investigates the composition of groundwater and leachate at a municipal waste landfill in southwestern Poland, two decades after its closure. The research, conducted in 2023, aimed to assess groundwater quality using 11 physico-chemical and 13 microplastic indicators. Groundwater and leachate samples were collected seasonally to assess of groundwater quality around landfill, including presence of heavy metals (Cd, Cr6+, Cu, Pb), PAHs and TOC, and microplastics. The results revealed persistent environmental degradation, with elevated concentrations of total organic carbon (24.8 mg/L) and cadmium (0.0211 mg/L), particularly in the second half of the year. Additionally, PET microplastics were detected in correlation with increased precipitation and leachate generation. These findings indicate that pollutants continue to migrate from the waste deposit into the surrounding groundwater, with seasonal patterns amplifying their presence. The study confirms that even decades after closure, municipal landfills can remain significant sources of both chemical and microplastic contamination, underlining the need for long-term monitoring and remediation strategies to protect groundwater resources. Full article
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12 pages, 3422 KiB  
Article
Quantitative Detection of Pyrene in Edible Oil via Plasmonic TLC-SERS Combined with Machine Learning Analysis
by Jiahui Tian, Xianhe Jiao, Jiaqi Guo, Qian Yu, Shuqin Zhang, Guizhou Gu, Kundan Sivashanmugan and Xianming Kong
Biosensors 2025, 15(8), 477; https://doi.org/10.3390/bios15080477 - 23 Jul 2025
Viewed by 319
Abstract
The presence of polycyclic aromatic hydrocarbons (PAHs) in edible oil has a serious effect on human health and may potentially induce cancer. This study combined thin-layer chromatography and surface-enhanced Raman spectroscopy (TLC-SERS) to rapidly and quantitatively detect PAHs in culinary oil. Machine learning [...] Read more.
The presence of polycyclic aromatic hydrocarbons (PAHs) in edible oil has a serious effect on human health and may potentially induce cancer. This study combined thin-layer chromatography and surface-enhanced Raman spectroscopy (TLC-SERS) to rapidly and quantitatively detect PAHs in culinary oil. Machine learning using the principle component analysis-back propagation neural network (PCA-BP) was integrated with TLC-SERS for the detection of PAHs. Ag nanoparticles on diatomite (diatomite/Ag) TLC-SERS substrate were prepared via an in situ growth process and employed as a stationary phase in the TLC channel. The analyte sample was dropped onto the TLC channel for separation and detection. The diatomite/Ag TLC channel demonstrated excellent separation capability and superior SERS performance and successfully detected PAHs from edible oil at a sensitivity of 0.1 ppm. The PCA-BP quantitative analysis model demonstrated outstanding prediction performance. This work demonstrates that the combination of TLC-SERS technology with PCA-BP is an efficient and accurate method for quantitatively detecting PAHs in edible oil, which can effectively improve the quality of food. Full article
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16 pages, 4298 KiB  
Article
Investigation of Flame Structure and PAHs’ Evolution in a Swirl-Stabilized Spray Flame at Elevated Pressure
by Wenyu Wang, Runfan Zhu, Siyu Liu, Yong He, Wubin Weng, Shixing Wang, William L. Roberts and Zhihua Wang
Energies 2025, 18(15), 3923; https://doi.org/10.3390/en18153923 - 23 Jul 2025
Viewed by 286
Abstract
Swirl spray combustion has attracted significant attention due to its common usage in gas turbines. However, the high pressure in many practical applications remains a major obstacle to the deep understanding of flame stability and pollutant formation. To address this concern, this study [...] Read more.
Swirl spray combustion has attracted significant attention due to its common usage in gas turbines. However, the high pressure in many practical applications remains a major obstacle to the deep understanding of flame stability and pollutant formation. To address this concern, this study investigated a swirl spray flame fueled with n-decane at elevated pressure. Planar laser-induced fluorescence (PLIF) of OH and polycyclic aromatic hydrocarbons (PAHs) were used simultaneously, enabling the distinction of the locations of OH, PAHs, and mixtures of them, providing detailed information on flame structure and evolution of PAHs. The effects of swirl number and ambient pressure on reaction zone characteristics and PAHs’ formation were studied, with the swirl number ranging from 0.30 to 1.18 and the pressure ranging from 1 to 3 bar. The data suggest that the swirl number changes the flame structure from V-shaped to crown-shaped, as observed at both atmospheric and elevated pressures. Additionally, varying swirl numbers lead to the initiation of flame divergence at distinct pressure levels. Moreover, PAHs of different molecular sizes exhibit significant overlap, with larger PAHs able to further extend downstream. The relative concentration of PAH increased with pressure, and the promoting effect of pressure on producing larger PAHs was significant. Full article
(This article belongs to the Special Issue Challenges and Opportunities in the Global Clean Energy Transition)
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9 pages, 418 KiB  
Review
The Occult Cascade That Leads to CTEPH
by Charli Fox and Lavannya M. Pandit
BioChem 2025, 5(3), 22; https://doi.org/10.3390/biochem5030022 - 23 Jul 2025
Viewed by 191
Abstract
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, progressive form of pre-capillary pulmonary hypertension characterized by persistent, organized thromboemboli in the pulmonary vasculature, leading to vascular remodeling, elevated pulmonary artery pressures, right heart failure, and significant morbidity and mortality if untreated. Despite advances, [...] Read more.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, progressive form of pre-capillary pulmonary hypertension characterized by persistent, organized thromboemboli in the pulmonary vasculature, leading to vascular remodeling, elevated pulmonary artery pressures, right heart failure, and significant morbidity and mortality if untreated. Despite advances, CTEPH remains underdiagnosed due to nonspecific symptoms and overlapping features with other forms of pulmonary hypertension. Basic Methodology: This review synthesizes data from large international registries, epidemiologic studies, translational research, and multicenter clinical trials. Key methodologies include analysis of registry data to assess incidence and risk factors, histopathological examination of lung specimens, and molecular studies investigating endothelial dysfunction and inflammatory pathways. Diagnostic modalities and treatment outcomes are evaluated through observational studies and randomized controlled trials. Recent Advances and Affected Population: Research has elucidated that CTEPH arises from incomplete resolution of pulmonary emboli, with subsequent fibrotic transformation mediated by dysregulated TGF-β/TGFBI signaling, endothelial dysfunction, and chronic inflammation. Affected populations are typically older adults, often with prior venous thromboembolism, splenectomy, or prothrombotic conditions, though up to 25% have no history of acute PE. The disease burden is substantial, with delayed diagnosis contributing to worse outcomes and higher societal costs. Microvascular arteriopathy and PAH-like lesions in non-occluded vessels further complicate the clinical picture. Conclusions: CTEPH is now recognized as a treatable disease, with multimodal therapies—surgical endarterectomy, balloon pulmonary angioplasty, and targeted pharmacotherapy—significantly improving survival and quality of life. Ongoing research into molecular mechanisms and biomarker-driven diagnostics promises earlier identification and more personalized management. Multidisciplinary care and continued translational investigation are essential to further reduce mortality and optimize outcomes for this complex patient population. Full article
(This article belongs to the Special Issue Feature Papers in BioChem, 2nd Edition)
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23 pages, 2483 KiB  
Article
A Unionid Mussel Biodiversity Hotspot Experiencing Unexplained Declines: Evaluating the Influence of Chemical Stressors Using Caged Juveniles
by W. Aaron Wilson, Christine Bergeron, Jennifer Archambault, Jason Unrine, Jess Jones, Braven Beaty, Damian Shea, Peter R. Lazaro, Jody L. Callihan, Jennifer J. Rogers and W. Gregory Cope
Diversity 2025, 17(8), 503; https://doi.org/10.3390/d17080503 - 22 Jul 2025
Viewed by 300
Abstract
Unionid mussel populations in a section of the Clinch River in Virginia, USA, has declined substantially, but the causes of the decline remain unknown. To investigate this zone of decline (ZOD), we deployed juvenile freshwater mussels (Villosa iris in 2012 and Lampsilis [...] Read more.
Unionid mussel populations in a section of the Clinch River in Virginia, USA, has declined substantially, but the causes of the decline remain unknown. To investigate this zone of decline (ZOD), we deployed juvenile freshwater mussels (Villosa iris in 2012 and Lampsilis fasciola in 2013) in both cages and silos at sites within the Clinch River System. We analyzed mussel tissues for trace element and organic contaminant concentrations, shells for trace elements, and environmental media (total water, dissolved water, particulate sediment, and bedload sediment) for both inorganic and organic contaminants. We found a few differences between mussels deployed in cages and those deployed in silos: survival was slightly lower in cages due to periodic sedimentation. Our results identified the ZOD based on the accumulation of trace elements (notably As, Cu, Fe, Mn, Ni, and Sr), polycyclic aromatic hydrocarbons (PAHs), and δ15N enrichment, with especially high concentrations found in the human-impacted tributaries, Dumps Creek and Guest River. Some correlations were found between environmental media and both mussel tissues and shells. In particular, PAHs and Mn had several significant relationships between bioaccumulated concentrations and environmental concentrations. Finally, Co, Cu, Fe, and V in soft tissues negatively correlated with mussel growth, whereas bioaccumulated PAH concentrations correlated negatively with resident mussel densities. Full article
(This article belongs to the Special Issue Freshwater Biodiversity Hotspots in 2025)
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12 pages, 1751 KiB  
Article
Causal Inference of Adverse Drug Events in Pulmonary Arterial Hypertension: A Pharmacovigilance Study
by Hongmei Li, Xiaojun He, Cui Chen, Qiao Ni, Linghao Ni, Jiawei Zhou and Bin Peng
Pharmaceuticals 2025, 18(8), 1084; https://doi.org/10.3390/ph18081084 - 22 Jul 2025
Viewed by 256
Abstract
Objective: Pulmonary arterial hypertension (PAH) is a progressive and life-threatening disease. Adverse events (AEs) related to its drug treatment seriously damaged the patient’s health. This study aims to clarify the causal relationship between PAH drugs and these AEs by combining pharmacovigilance signal detection [...] Read more.
Objective: Pulmonary arterial hypertension (PAH) is a progressive and life-threatening disease. Adverse events (AEs) related to its drug treatment seriously damaged the patient’s health. This study aims to clarify the causal relationship between PAH drugs and these AEs by combining pharmacovigilance signal detection with the Bayesian causal network model. Methods: Patient data were obtained from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), covering reports from 2013 to 2023. In accordance with standard pharmacovigilance methodologies, disproportionality analysis was performed to detect signals. Target drugs were selected based on the following criteria: number of reports (a) ≥ 3, proportional reporting ratio (PRR) ≥ 2, and chi-square (χ2) ≥ 4. Bayesian causal network models were then constructed to estimate causal relationships. The do-calculus and adjustment formula were applied to calculate the causal effects between drugs and AEs. Results: Signal detection revealed that Ambrisentan, Bosentan, and Iloprost were associated with serious AEs, including death, dyspnea, pneumonia, and edema. For Ambrisentan, the top-ranked adverse drug events (ADEs) based on average causal effect (ACE) were peripheral swelling (ACE = 0.032) and anemia (ACE = 0.021). For Iloprost, the most prominent ADE was hyperthyroidism (ACE = 0.048). Conclusions: This study quantifies causal drug–event relationships in PAH using Bayesian causal networks. The findings offer valuable evidence regarding the clinical safety of PAH medications, thereby improving patient health outcomes. Full article
(This article belongs to the Section Pharmacology)
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11 pages, 892 KiB  
Article
Sotatercept for Connective Tissue Disease-Associated Pulmonary Arterial Hypertension with Concomitant Interstitial Lung Disease: Efficacy and Safety Insights
by Chebly Dagher, Maria Akiki, Kristin Swanson, Brett Carollo, Garett Fiscus, Harrison W. Farber and Raj Parikh
J. Clin. Med. 2025, 14(15), 5177; https://doi.org/10.3390/jcm14155177 - 22 Jul 2025
Viewed by 385
Abstract
Background/Objectives: Sotatercept has demonstrated efficacy in pulmonary arterial hypertension (PAH), but its use has not been studied in patients with Group 3 pulmonary hypertension (PH). Additionally, patients with connective tissue disease-associated PAH (CTD-PAH) were underrepresented in the STELLAR trial. Given the limited [...] Read more.
Background/Objectives: Sotatercept has demonstrated efficacy in pulmonary arterial hypertension (PAH), but its use has not been studied in patients with Group 3 pulmonary hypertension (PH). Additionally, patients with connective tissue disease-associated PAH (CTD-PAH) were underrepresented in the STELLAR trial. Given the limited treatment options for pulmonary hypertension in patients with interstitial lung disease (PH-ILD), this study aimed to evaluate the use of sotatercept in CTD-PAH patients with concomitant ILD. Methods: Eligible patients (n = 7) had a confirmed diagnosis of CTD-PAH with concomitant ILD. The patients were already receiving background PAH therapy. Baseline hemodynamic and clinical measurements were reassessed after 24 weeks of sotatercept therapy. The variables assessed included six-minute walk distance (6MWD), pulmonary vascular resistance (PVR), echocardiographic right ventricular systolic pressure (eRVSP), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, World Health Organization (WHO) functional class, and supplemental oxygen requirements. Results: The study included seven patients with a mean age of 57 years (range: 39–73 years). After 24 weeks, the mean 6MWT distance increased from 211 m to 348 m (p < 0.01). Mean PVR decreased from 7.77 WU at baseline to 4.53 WU (p < 0.01). Mean eRVSP decreased from 79.43 mmHg to 54.14 mmHg (p < 0.01). NT-proBNP decreased from 3056.86 pg/mL to 1404.29 pg/mL (p < 0.01). The WHO functional class and supplemental oxygen requirements improved in all patients. Conclusions: Sotatercept was tolerated in patients with CTD-PAH and ILD, with no evidence of adverse respiratory effects. When added to foundational PAH therapy, sotatercept resulted in significant improvements across multiple parameters. These findings suggest that sotatercept may be a promising therapeutic option as an adjunctive treatment in this patient population. Full article
(This article belongs to the Section Respiratory Medicine)
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