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25 pages, 2916 KiB  
Review
Navigating the Depths: A Comprehensive Review of 40 Years of Marine Oil Pollution Studies in the Philippines (1980 to 2024)
by Hernando P. Bacosa, Jill Ruby L. Parmisana, Nur Inih U. Sahidjan, Joevin Mar B. Tumongha, Keana Aubrey A. Valdehueza, Jay Rumen U. Maglupay, Andres Philip Mayol, Chin-Chang Hung, Marianne Faith Martinico-Perez, Kozo Watanabe, Mei-Fang Chien and Chihiro Inoue
Water 2025, 17(11), 1709; https://doi.org/10.3390/w17111709 - 4 Jun 2025
Viewed by 1534
Abstract
This review synthesizes four decades (1980–2024) of marine oil spill research in the Philippines, analyzing 80 peer-reviewed publications sourced from Scopus, Web of Science, Clarivate, and Google Scholar. Findings show that oil spill research activity spikes after major spills, particularly the 2006 Guimaras [...] Read more.
This review synthesizes four decades (1980–2024) of marine oil spill research in the Philippines, analyzing 80 peer-reviewed publications sourced from Scopus, Web of Science, Clarivate, and Google Scholar. Findings show that oil spill research activity spikes after major spills, particularly the 2006 Guimaras incident, which accounts for over half of the reviewed studies and were mostly concentrated in the field of biology, followed by social sciences. Mangroves are the most studied as they are the widely affected ecosystem in the Philippines. Despite the number of published articles on oil spills in the Philippines, only the major events were emphasized, and small-scale spills remain under documented. Research on small-scale oil spills and the country’s two recent big oil spills (Mindoro Oil Spill and Manila Bay Oil Spill), particularly in a country’s environmentally sensitive areas, must be conducted in collaboration with academic institutions and relevant stakeholders to gain a deeper understanding and formulate appropriate countermeasures in the event of future spills. The review also highlights limited application of advanced techniques such as hydrocarbon fingerprinting, geospatial analysis, and next-generation DNA sequencing, limiting comprehensive assessments of oil fate and ecological effects. Addressing these gaps through interdisciplinary collaboration is critical to improving oil spill response, environmental management, and policy formulation in the Philippines’ complex archipelagic setting. Full article
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22 pages, 2615 KiB  
Article
Degradation of 1,4-Dioxane by Au/TiO2 Janus Nanoparticles Under Ultraviolet Light: Experiments and Modeling
by Yangyuan Ji, Matthew J. Tao, Lamar O. Mair, Amit Kumar Singh, Yuhang Fang, Sathish Rajendran, Thomas E. Beechem, David M. Warsinger and Jeffrey L. Moran
Water 2025, 17(11), 1708; https://doi.org/10.3390/w17111708 - 4 Jun 2025
Viewed by 684
Abstract
Advanced oxidation processes (AOPs) show significant promise to degrade recalcitrant water contaminants, such as 1,4-dioxane, but slow degradation kinetics limit the energy efficiency of this technology. We realized substantial enhancements in the degradation of 1,4-dioxane (a suspected carcinogen) using gold-coated titanium dioxide (Au/TiO [...] Read more.
Advanced oxidation processes (AOPs) show significant promise to degrade recalcitrant water contaminants, such as 1,4-dioxane, but slow degradation kinetics limit the energy efficiency of this technology. We realized substantial enhancements in the degradation of 1,4-dioxane (a suspected carcinogen) using gold-coated titanium dioxide (Au/TiO2) Janus nanoparticles (JNPs) irradiated with above-bandgap ultraviolet (UV) light (peak wavelength, 254 nm). To explain this result, we combined experimental measurements quantifying 1,4-dioxane degradation at varying UV wavelengths with finite-element simulations that provided explanatory insight into the light–matter interactions at play. The enhanced photocatalytic activity at the optimal condition (254 nm light, high intensity, Au/TiO2) resulted from a larger quantity of photogenerated holes in the TiO2 capable of reacting with water to form hydroxyl radicals that degrade 1,4-dioxane. This increased production of holes resulted from two sources: (1) more viable electron–hole pairs were created under 254 nm light owing to increased light absorption by the TiO2 that was localized near the surface; (2) the metal sequestered photogenerated electrons from the TiO2, which prevented electron–hole pairs from recombining, leaving more holes available to react with water. Our results motivate the exploration of different metal coatings (especially non-precious metals) and suggest a path toward broader implementation of TiO2-based photocatalytic AOPs, which can effectively remove many water pollutants that survive conventional treatment techniques. Full article
(This article belongs to the Special Issue Water Treatment Technology for Emerging Contaminants, 2nd Edition)
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14 pages, 5770 KiB  
Article
Low CD25 in ALK+ Anaplastic Large Cell Lymphoma Is Associated with Older Age, Thrombocytopenia, and Increased Expression of Surface CD3 and CD8
by Shuyu E, L. Jeffrey Medeiros, Hong Fang, Shaoying Li, Guilin Tang, Sa A. Wang, Wei Wang, C. Cameron Yin, M. James You, Swaminathan P. Iyer, Luis Malpica, Lianqun Qiu, Zhenya Tang, Qing Wei, Pei Lin and Jie Xu
Cancers 2025, 17(11), 1767; https://doi.org/10.3390/cancers17111767 - 25 May 2025
Viewed by 532
Abstract
Background/Objectives: Anaplastic lymphoma kinase (ALK)-positive (+) anaplastic large cell lymphoma (ALCL) is known to express CD25, but its significance has not been well studied. Methods: In the present study, we identified 54 ALK+ ALCL patients with CD25 results available and investigated the significance [...] Read more.
Background/Objectives: Anaplastic lymphoma kinase (ALK)-positive (+) anaplastic large cell lymphoma (ALCL) is known to express CD25, but its significance has not been well studied. Methods: In the present study, we identified 54 ALK+ ALCL patients with CD25 results available and investigated the significance of CD25 expression levels. Results: Forty-two (78%) cases had high CD25 expressions, whereas low CD25 expressions were found in 12 (22%) cases. Compared with ALK+ ALCL patients with CD25-high neoplasms, patients with CD25-low neoplasms were older (median: 40 years vs. 29 years, p = 0.01) and more often had thrombocytopenia (40% vs. 0%, p = 0.02). Between CD25-low and CD25-high groups, other clinical features were similar to each other (all p > 0.05). CD25-low ALK+ ALCL cases showed higher frequency of surface CD3 (100% vs. 3%, p = 0.001) and CD8 (57% vs. 14%, p = 0.03). Fourteen of 47 (30%) ALK+ ALCL patients died (median follow-up time, 33.8 months; range, 0.3–382.8 months): 5 of 9 (56%) patients with CD25-low neoplasms and 9 of 38 (24%) patients with CD25-high neoplasms. Univariate analysis showed: (1) the OS of patients with CD25-low ALK+ ALCL was shorter than that of patients with CD25-high ALK+ ALCL (median: 72.2 months vs. undefined, p = 0.02); and (2) young (<30 years) patients with high CD25 expression had the best prognosis, with a long-term OS rate of 89%. However, in multivariate analysis, low CD25 expression did not significantly impact OS. Conclusions: most cases of ALK+ ALCL highly express CD25 which is a potential target for therapy. ALK+ ALCL with low CD25 expression is associated with older patient age and increased frequency of thrombocytopenia and surface CD3 and CD8 expression. Full article
(This article belongs to the Special Issue Advances in Pathology of Lymphoma and Leukemia)
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22 pages, 8798 KiB  
Article
Climate Warming-Induced Hydrological Regime Shifts in Cold Northeast Asia: Insights from the Heilongjiang-Amur River Basin
by Jiaoyang Li, Ruixin Wang, Qiwei Huang, Jun Xia, Ping Wang, Yuanhao Fang, Vladimir V. Shamov, Natalia L. Frolova and Dunxian She
Land 2025, 14(5), 980; https://doi.org/10.3390/land14050980 - 1 May 2025
Viewed by 437
Abstract
Rapid climate warming and intensified human activities are causing profound alterations in terrestrial hydrological systems. Understanding shifts in hydrological regimes and the underlying mechanisms driving these changes is crucial for effective water resource management, watershed planning, and flood disaster mitigation. This study examines [...] Read more.
Rapid climate warming and intensified human activities are causing profound alterations in terrestrial hydrological systems. Understanding shifts in hydrological regimes and the underlying mechanisms driving these changes is crucial for effective water resource management, watershed planning, and flood disaster mitigation. This study examines the hydrological regimes of the Heilongjiang-Amur River Basin, a transboundary river basin characterized by extensive permafrost distribution in northeastern Asia, by analyzing long-term daily meteorological (temperature, precipitation, evaporation) and hydrological data from the Komsomolsk, Khabarovsk, and Bogorodskoye stations. Missing daily runoff data were reconstructed using three machine learning methods: Convolutional Neural Networks (CNN), Long Short-Term Memory Networks (LSTM), and Convolutional Long Short-Term Memory Networks (CNN-LSTM). Trend analysis, abrupt change detection, and regression techniques revealed significant warming and increased actual evapotranspiration in the basin from 1950 to 2022, whereas precipitation and snow water equivalent showed no significant trends. Climate warming is significantly altering hydrological regimes by changing precipitation patterns and accelerating permafrost thaw. At the Komsomolsk station, an increase of 1 mm in annual precipitation resulted in a 0.48 mm rise in annual runoff depth, while a 1 °C rise in temperature led to an increase of 1.65 mm in annual runoff depth. Although annual runoff exhibited no significant long-term trend, low-flow runoff demonstrated substantial increases, primarily driven by temperature and precipitation. These findings provide critical insights into the hydrological responses of permafrost-dominated river basins to climate change, offering a scientific basis for sustainable water resource management and strategies to mitigate climate-induced hydrological risks. Full article
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22 pages, 1223 KiB  
Article
Association Between B-Cell Marker Expression and RUNX1 Lesions in Acute Myeloid Leukemia, Beyond RUNX1::RUNX1T1 Fusion: Diagnostic Pitfalls with Mixed-Phenotype Acute Leukemia—B/Myeloid
by Giby V. George, Malgorzata Kajstura, Audrey N. Jajosky, Hong Fang, Fatima Zahra Jelloul, Andrew G. Evans, W. Richard Burack, John M. Bennett, L. Jeffrey Medeiros, Wei Wang and Siba El Hussein
Cancers 2025, 17(8), 1354; https://doi.org/10.3390/cancers17081354 - 18 Apr 2025
Viewed by 880
Abstract
Acute myeloid leukemia (AML) with RUNX1::RUNX1T1 fusion is well known to often demonstrate aberrant upregulation of CD19 expression. We studied the clinicopathologic and genetic features of 16 cases of AML with various RUNX1 lesions, including mutations, copy number gains, and translocations [...] Read more.
Acute myeloid leukemia (AML) with RUNX1::RUNX1T1 fusion is well known to often demonstrate aberrant upregulation of CD19 expression. We studied the clinicopathologic and genetic features of 16 cases of AML with various RUNX1 lesions, including mutations, copy number gains, and translocations other than fusions with RUNX1T1. Most of these cases were classified as AML-myelodysplasia-related or AML-post-cytotoxic therapy based on the cytogenetic and molecular work-up. These neoplasms showed partial expression of one or more B-cell antigens by flow cytometry and/or immunohistochemistry, fulfilling the criteria for mixed-phenotype acute leukemia (MPAL)-B/myeloid (i.e., ≥20% blasts expressing B and myeloid lineage antigens) in most cases. These findings suggest that AML cases with RUNX1 lesions including mutations, copy number gains, and translocations other than RUNX1T1 fusion, also commonly express B-cell markers, imparting a “mixed-lineage-like” immunophenotype in cases of AML that otherwise fulfill the criteria for other defined subtypes. We present these cases as to caution regarding this potential diagnostic pitfall and favor a diagnosis of AML with RUNX1 lesion(s) in the setting of a case of AML with myeloid/B-cell antigen expression, a history of myelodysplasia or cytotoxic therapy, the demonstration of pDC differentiation by flow cytometry (generally associated with the presence of a RUNX1 mutation), and the presence of a RUNX1 lesion (mutation, copy number gain, and/or translocation exclusive of a rearrangement with RUNX1T1). Full article
(This article belongs to the Special Issue Advances in Pathology of Lymphoma and Leukemia)
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29 pages, 3514 KiB  
Review
Mesoplastics: A Review of Contamination Status, Analytical Methods, Pollution Sources, Potential Risks, and Future Perspectives of an Emerging Global Environmental Pollutant
by Dioniela Mae C. Ellos, Mei-Fang Chien, Chihiro Inoue, Haruka Nakano, Atsuhiko Isobe, Deo Florence L. Onda, Kozo Watanabe and Hernando P. Bacosa
Toxics 2025, 13(3), 227; https://doi.org/10.3390/toxics13030227 - 20 Mar 2025
Viewed by 1619
Abstract
Mesoplastics are emerging environmental pollutants that can pose a threat to the environment. Researching mesoplastics is crucial as they bridge the gap between macroplastics and microplastics by determining their role in plastic fragmentation and pathways, as well as their ecological impact. Investigating mesoplastic [...] Read more.
Mesoplastics are emerging environmental pollutants that can pose a threat to the environment. Researching mesoplastics is crucial as they bridge the gap between macroplastics and microplastics by determining their role in plastic fragmentation and pathways, as well as their ecological impact. Investigating mesoplastic sources will help develop targeted policies and mitigation strategies to address plastic pollution. These pollutants are found across aquatic, terrestrial, and agricultural ecosystems. Unlike microplastics, mesoplastics are reviewed in the scientific literature. This paper focuses on existing published research on mesoplastics, determining the trends and synthesizing key findings related to mesoplastic pollution. Research primarily focused on marine and freshwater ecosystems, with surface water and beach sediments being the most studied compartments. Mesoplastics research often offers baseline data, with increased publications from 2014 to 2024, particularly in East Asia. However, certain ecosystems and regions remain underrepresented. Also, mesoplastics can disrupt ecosystems by degrading biodiversity, contaminating soils and waters, and affecting food chains. Mesoplastics can also become vectors for additives and pathogenic microorganisms, highlighting their environmental risks. Various factors influence mesoplastics’ prevalence, including anthropogenic and non-anthropogenic activities. With this, future research should expand into less-studied ecosystems and regions, explore mesoplastic interactions with pollutants and organisms, and promote public awareness, education, and policy measures to reduce plastic use and mitigate pollution globally. Full article
(This article belongs to the Special Issue Environmental Toxicology and Risk Assessment of Priority Substances)
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14 pages, 2258 KiB  
Article
Effects of Fentanyl-Laced Cocaine on Circulating Ghrelin, Insulin, and Glucose Levels in Rats
by Huimei Wei, Elise C. Maul, Annet Kyomuhangi, Shawn Park, Maddilynn L. Mutchler, Chang-Guo Zhan and Fang Zheng
Int. J. Mol. Sci. 2025, 26(5), 2341; https://doi.org/10.3390/ijms26052341 - 6 Mar 2025
Viewed by 959
Abstract
Opioid mixed with cocaine has been increasingly implicated in overdose deaths, including both intentional co-use of opioid and cocaine and fentanyl-adulterated drug supply. As ghrelin plays an important role in drug reward and can also influence insulin, this study aimed to assess responses [...] Read more.
Opioid mixed with cocaine has been increasingly implicated in overdose deaths, including both intentional co-use of opioid and cocaine and fentanyl-adulterated drug supply. As ghrelin plays an important role in drug reward and can also influence insulin, this study aimed to assess responses of the circulating ghrelin, insulin, and glucose levels to the combined use of fentanyl and cocaine (a polydrug) in rats by performing combined animal behavioral experiments and biochemical analysis. The experimental data consistently revealed that the fentanyl and cocaine co-use can significantly elevate both the acyl-ghrelin and desacyl-ghrelin levels and significantly decrease the insulin level without significant effects on the glucose level. These findings suggest that, like cocaine itself, the fentanyl–cocaine polydrug can self-promote its rewarding effects via elevating the ghrelin level, and that the ghrelin system might serve as a potential pharmacological target for treatment of substance use disorders caused by polysubstance use involving fentanyl and cocaine. Additionally, based on the insulin data obtained in this study, the insulin level was always downregulated significantly and considerably, implying that the fentanyl and cocaine polydrug might have a stronger cardiovascular toxicity to the patients with insulin resistance and diabetes. Further studies are required to examine this possibility. Full article
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16 pages, 3897 KiB  
Article
Divergent Requirements for Glutathione Biosynthesis During Osteoclast Differentiation In Vitro and In Vivo
by Guoli Hu, Amy L. Whitaker, Guo-Fang Zhang and Courtney M. Karner
Antioxidants 2025, 14(2), 197; https://doi.org/10.3390/antiox14020197 - 10 Feb 2025
Cited by 1 | Viewed by 1217
Abstract
Glutathione (GSH) is the most abundant antioxidant in the cell, and it is responsible for neutralizing reactive oxygen species (ROS). ROS can promote osteoclast differentiation and stimulate bone resorption and are some of the primary drivers of bone loss with aging and loss [...] Read more.
Glutathione (GSH) is the most abundant antioxidant in the cell, and it is responsible for neutralizing reactive oxygen species (ROS). ROS can promote osteoclast differentiation and stimulate bone resorption and are some of the primary drivers of bone loss with aging and loss of sex steroids. Despite this, the role of GSH biosynthesis during osteoclastogenesis remains controversial. Here, we show that the requirements for GSH biosynthesis during osteoclastogenesis in vitro and in vivo are unique. Using a metabolomics approach, we discovered that both oxidative stress and GSH biosynthesis increase during osteoclastogenesis. Inhibiting GSH biosynthesis in vitro via the pharmacological or genetic inhibition of glutamate cysteine ligase (GCLC) prevented osteoclast differentiation. Conversely, the genetic ablation of GCLC in myeloid cells using LysMCre resulted in a decrease in bone mass in both male and female mice. The decreased bone mass of the LysMCre;Gclcfl/fl mice was attributed to increased osteoclast numbers and elevated bone resorption. Collectively, our data provide strong genetic evidence that GSH biosynthesis is essential for the regulation of osteoclast differentiation and bone resorption in mice. Moreover, these findings highlight the necessity of complementing in vitro studies with in vivo genetic studies. Full article
(This article belongs to the Special Issue Role of Nrf2 and ROS in Bone Metabolism)
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13 pages, 2212 KiB  
Article
Effect of Adapted Ergometer Setup and Rowing Speed on Lower Extremity Loading in People with and Without Spinal Cord Injury
by Ying Fang and Karen L. Troy
Bioengineering 2025, 12(1), 75; https://doi.org/10.3390/bioengineering12010075 - 15 Jan 2025
Viewed by 1131
Abstract
Background: Functional electrical stimulation-assisted rowing (FES rowing) is a rehabilitation exercise used to prevent disuse osteoporosis, which is common in people with spinal cord injury (SCI). However, its effect on bone loss prevention varied in SCI patients, potentially due to inconsistent loading. This [...] Read more.
Background: Functional electrical stimulation-assisted rowing (FES rowing) is a rehabilitation exercise used to prevent disuse osteoporosis, which is common in people with spinal cord injury (SCI). However, its effect on bone loss prevention varied in SCI patients, potentially due to inconsistent loading. This study investigates the effect of ergometer setup and rowing speed on lower extremity loading during rowing. Methods: Twenty able-bodied participants and one participant with SCI rowed on an adapted ergometer with different speeds and setups. We calculated foot reaction force and knee moment for all participants, and tibiofemoral force for the rower with SCI. Results: Able-bodied rowers generated 0.22–0.45 body weight (BW) foot reaction forces, and a higher force was associated with a fast speed, forward seat position, and large knee range of motion (RoM). The rower with SCI had the greatest foot reaction force (0.39 BW) when rowing with a small knee RoM at a rear seat position, and the highest tibiofemoral force (2.23 BW) with a large knee RoM or at a rear seat position. Conclusions: Ergometer setup and speed both affect lower limb loading and should be further studied in more rowers with SCI. This can inform rehabilitation protocols to standardize ergometer configuration to improve bone health. Full article
(This article belongs to the Special Issue Biomechanics of Orthopaedic Rehabilitation)
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15 pages, 7578 KiB  
Article
Optical Genome Mapping for Detection of BCR::ABL1—Another Tool in Our Toolbox
by Zhenya Tang, Wei Wang, Gokce A. Toruner, Shimin Hu, Hong Fang, Jie Xu, M. James You, L. Jeffrey Medeiros, Joseph D. Khoury and Guilin Tang
Genes 2024, 15(11), 1357; https://doi.org/10.3390/genes15111357 - 22 Oct 2024
Cited by 2 | Viewed by 1326
Abstract
Background: BCR::ABL1 fusion is mostly derived from a reciprocal translocation t(9;22)(q34.1;q11.2) and is rarely caused by insertion. Various methods have been used for the detection of t(9;22)/BCR::ABL1, such as G-banded chromosomal analysis, fluorescence in situ hybridization (FISH), quantitative real-time reverse [...] Read more.
Background: BCR::ABL1 fusion is mostly derived from a reciprocal translocation t(9;22)(q34.1;q11.2) and is rarely caused by insertion. Various methods have been used for the detection of t(9;22)/BCR::ABL1, such as G-banded chromosomal analysis, fluorescence in situ hybridization (FISH), quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and optical genome mapping (OGM). Understanding the strengths and limitations of each method is essential for the selection of appropriate method(s) of disease diagnosis and/or during the follow-up. Methods: We compared the results of OGM, chromosomal analysis, FISH, and/or RT-PCR in 12 cases with BCR::ABL1. Results: BCR:ABL1 was detected by FISH and RT-PCR in all 12 cases. One case with ins(22;9)/BCR::ABL1 was cryptic by chromosomal analysis and nearly missed by OGM. Atypical FISH signal patterns were observed in five cases, suggesting additional chromosomal aberrations involving chromosomes 9 and/or 22. RT-PCR identified the transcript isoforms p210 and p190 in seven and five cases, respectively. Chromosomal analysis revealed additional chromosomal aberrations in seven cases. OGM identified extra cytogenomic abnormalities in 10 cases, including chromoanagenesis and IKZF1 deletion, which were only detected by OGM. Conclusions: FISH offers rapid and definitive detection of BCR::ABL1 fusion, while OGM provides a comprehensive cytogenomic analysis. In scenarios where OGM is feasible, chromosomal analysis and RT-PCR may not offer additional diagnostic value. Full article
(This article belongs to the Special Issue Clinical Molecular Genetics in Hematologic Diseases)
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22 pages, 3369 KiB  
Article
The Loss of PPARγ Expression and Signaling Is a Key Feature of Cutaneous Actinic Disease and Squamous Cell Carcinoma: Association with Tumor Stromal Inflammation
by Raymond L. Konger, Xiaoling Xuei, Ethel Derr-Yellin, Fang Fang, Hongyu Gao and Yunlong Liu
Cells 2024, 13(16), 1356; https://doi.org/10.3390/cells13161356 - 15 Aug 2024
Cited by 1 | Viewed by 1987
Abstract
Given the importance of peroxisome proliferator-activated receptor (PPAR)-gamma in epidermal inflammation and carcinogenesis, we analyzed the transcriptomic changes observed in epidermal PPARγ-deficient mice (Pparg-/-epi). A gene set enrichment analysis revealed a close association with epithelial malignancy, inflammatory cell chemotaxis, [...] Read more.
Given the importance of peroxisome proliferator-activated receptor (PPAR)-gamma in epidermal inflammation and carcinogenesis, we analyzed the transcriptomic changes observed in epidermal PPARγ-deficient mice (Pparg-/-epi). A gene set enrichment analysis revealed a close association with epithelial malignancy, inflammatory cell chemotaxis, and cell survival. Single-cell sequencing of Pparg-/-epi mice verified changes to the stromal compartment, including increased inflammatory cell infiltrates, particularly neutrophils, and an increase in fibroblasts expressing myofibroblast marker genes. A comparison of transcriptomic data from Pparg-/-epi and publicly available human and/or mouse actinic keratoses (AKs) and cutaneous squamous cell carcinomas (SCCs) revealed a strong correlation between the datasets. Importantly, PPAR signaling was the top common inhibited canonical pathway in AKs and SCCs. Both AKs and SCCs also had significantly reduced PPARG expression and PPARγ activity z-scores. Smaller reductions in PPARA expression and PPARα activity and increased PPARD expression but reduced PPARδ activation were also observed. Reduced PPAR activity was also associated with reduced PPARα/RXRα activity, while LPS/IL1-mediated inhibition of RXR activity was significantly activated in the tumor datasets. Notably, these changes were not observed in normal sun-exposed skin relative to non-exposed skin. Finally, Ppara and Pparg were heavily expressed in sebocytes, while Ppard was highly expressed in myofibroblasts, suggesting that PPARδ has a role in myofibroblast differentiation. In conclusion, these data provide strong evidence that PPARγ and possibly PPARα represent key tumor suppressors by acting as master inhibitors of the inflammatory changes found in AKs and SCCs. Full article
(This article belongs to the Special Issue The Role of PPARs in Disease - Volume III)
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11 pages, 821 KiB  
Brief Report
Association of PHACTR1 with Coronary Artery Calcium Differs by Sex and Cigarette Smoking
by Kirsten Voorhies, Kendra Young, Fang-Chi Hsu, Nicholette D. Palmer, Merry-Lynn N. McDonald, Sanghun Lee, Georg Hahn, Julian Hecker, Dmitry Prokopenko, Ann Chen Wu, Elizabeth A. Regan, Dawn DeMeo, Greg L. Kinney, James D. Crapo, Michael H. Cho, Edwin K. Silverman, Christoph Lange, Matthew J. Budoff, John E. Hokanson and Sharon M. Lutz
J. Cardiovasc. Dev. Dis. 2024, 11(7), 194; https://doi.org/10.3390/jcdd11070194 - 27 Jun 2024
Viewed by 2579
Abstract
Background: Coronary artery calcium (CAC) is a marker of subclinical atherosclerosis and is a complex heritable trait with both genetic and environmental risk factors, including sex and smoking. Methods: We performed genome-wide association (GWA) analyses for CAC among all participants and stratified by [...] Read more.
Background: Coronary artery calcium (CAC) is a marker of subclinical atherosclerosis and is a complex heritable trait with both genetic and environmental risk factors, including sex and smoking. Methods: We performed genome-wide association (GWA) analyses for CAC among all participants and stratified by sex in the COPDGene study (n = 6144 participants of European ancestry and n = 2589 participants of African ancestry) with replication in the Diabetes Heart Study (DHS). We adjusted for age, sex, current smoking status, BMI, diabetes, self-reported high blood pressure, self-reported high cholesterol, and genetic ancestry (as summarized by principal components computed within each racial group). For the significant signals from the GWA analyses, we examined the single nucleotide polymorphism (SNP) by sex interactions, stratified by smoking status (current vs. former), and tested for a SNP by smoking status interaction on CAC. Results: We identified genome-wide significant associations for CAC in the chromosome 9p21 region [CDKN2B-AS1] among all COPDGene participants (p = 7.1 × 10−14) and among males (p = 1.0 × 10−9), but the signal was not genome-wide significant among females (p = 6.4 × 10−6). For the sex stratified GWA analyses among females, the chromosome 6p24 region [PHACTR1] had a genome-wide significant association (p = 4.4 × 10−8) with CAC, but this signal was not genome-wide significant among all COPDGene participants (p = 1.7 × 10−7) or males (p = 0.03). There was a significant interaction for the SNP rs9349379 in PHACTR1 with sex (p = 0.02), but the interaction was not significant for the SNP rs10757272 in CDKN2B-AS1 with sex (p = 0.21). In addition, PHACTR1 had a stronger association with CAC among current smokers (p = 6.2 × 10−7) than former smokers (p = 7.5 × 10−3) and the SNP by smoking status interaction was marginally significant (p = 0.03). CDKN2B-AS1 had a strong association with CAC among both former (p = 7.7 × 10−8) and current smokers (p = 1.7 × 10−7) and the SNP by smoking status interaction was not significant (p = 0.40). Conclusions: Among current and former smokers of European ancestry in the COPDGene study, we identified a genome-wide significant association in the chromosome 6p24 region [PHACTR1] with CAC among females, but not among males. This region had a significant SNP by sex and SNP by smoking interaction on CAC. Full article
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15 pages, 960 KiB  
Article
Postprandial Plasma Glucose between 4 and 7.9 h May Be a Potential Diagnostic Marker for Diabetes
by Yutang Wang, Yan Fang, Christopher L. Aberson, Fadi J. Charchar and Antonio Ceriello
Biomedicines 2024, 12(6), 1313; https://doi.org/10.3390/biomedicines12061313 - 13 Jun 2024
Cited by 2 | Viewed by 2279
Abstract
Postprandial glucose levels between 4 and 7.9 h (PPG4–7.9h) correlate with mortality from various diseases, including hypertension, diabetes, cardiovascular disease, and cancer. This study aimed to assess if predicted PPG4–7.9h could diagnose diabetes. Two groups of participants were involved: Group [...] Read more.
Postprandial glucose levels between 4 and 7.9 h (PPG4–7.9h) correlate with mortality from various diseases, including hypertension, diabetes, cardiovascular disease, and cancer. This study aimed to assess if predicted PPG4–7.9h could diagnose diabetes. Two groups of participants were involved: Group 1 (4420 participants) had actual PPG4–7.9h, while Group 2 (8422 participants) lacked this measure but had all the diabetes diagnostic measures. Group 1 underwent multiple linear regression to predict PPG4–7.9h using 30 predictors, achieving accuracy within 11.1 mg/dL in 80% of the participants. Group 2 had PPG4–7.9h predicted using this model. A receiver operating characteristic curve analysis showed that predicted PPG4–7.9h could diagnose diabetes with an accuracy of 87.3% in Group 2, with a sensitivity of 75.1% and specificity of 84.1% at the optimal cutoff of 102.5 mg/dL. A simulation on 10,000 random samples from Group 2 revealed that 175 participants may be needed to investigate PPG4–7.9h as a diabetes diagnostic marker with a power of at least 80%. In conclusion, predicted PPG4–7.9h appears to be a promising diagnostic indicator for diabetes. Future studies seeking to ascertain its definitive diagnostic value might require a minimum sample size of 175 participants. Full article
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19 pages, 1250 KiB  
Article
Parafoveal Processing of Orthography, Phonology, and Semantics during Chinese Reading: Effects of Foveal Load
by Lei Zhang, Liangyue Kang, Wanying Chen, Fang Xie and Kayleigh L. Warrington
Brain Sci. 2024, 14(5), 512; https://doi.org/10.3390/brainsci14050512 - 18 May 2024
Cited by 1 | Viewed by 1628
Abstract
The foveal load hypothesis assumes that the ease (or difficulty) of processing the currently fixated word in a sentence can influence processing of the upcoming word(s), such that parafoveal preview is reduced when foveal load is high. Recent investigations using pseudo-character previews reported [...] Read more.
The foveal load hypothesis assumes that the ease (or difficulty) of processing the currently fixated word in a sentence can influence processing of the upcoming word(s), such that parafoveal preview is reduced when foveal load is high. Recent investigations using pseudo-character previews reported an absence of foveal load effects in Chinese reading. Substantial Chinese studies to date provide some evidence to show that parafoveal words may be processed orthographically, phonologically, or semantically. However, it has not yet been established whether parafoveal processing is equivalent in terms of the type of parafoveal information extracted (orthographic, phonological, semantic) under different foveal load conditions. Accordingly, the present study investigated this issue with two experiments. Participants’ eye movements were recorded as they read sentences in which foveal load was manipulated by placing a low- or high-frequency word N preceding a critical word. The preview validity of the upcoming word N + 1 was manipulated in Experiment 1, and word N + 2 in Experiment 2. The parafoveal preview was either identical to word N + 1(or word N + 2); orthographically related; phonologically related; semantically related; or an unrelated pseudo-character. The results showed robust main effects of frequency and preview type on both N + 1 and N + 2. Crucially, however, interactions between foveal load and preview type were absent, indicating that foveal load does not modulate the types of parafoveal information processed during Chinese reading. Full article
(This article belongs to the Section Neurolinguistics)
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14 pages, 3678 KiB  
Article
Normalized Clinical Severity Scores Reveal a Correlation between X Chromosome Inactivation and Disease Severity in Rett Syndrome
by Jonathan K. Merritt, Xiaolan Fang, Raymond C. Caylor, Steven A. Skinner, Michael J. Friez, Alan K. Percy and Jeffrey L. Neul
Genes 2024, 15(5), 594; https://doi.org/10.3390/genes15050594 - 8 May 2024
Cited by 2 | Viewed by 2046
Abstract
Rett Syndrome (RTT) is a severe neurodevelopmental disorder predominately diagnosed in females and primarily caused by pathogenic variants in the X-linked gene Methyl-CpG Binding Protein 2 (MECP2). Most often, the disease causing the MECP2 allele resides on the paternal X chromosome [...] Read more.
Rett Syndrome (RTT) is a severe neurodevelopmental disorder predominately diagnosed in females and primarily caused by pathogenic variants in the X-linked gene Methyl-CpG Binding Protein 2 (MECP2). Most often, the disease causing the MECP2 allele resides on the paternal X chromosome while a healthy copy is maintained on the maternal X chromosome with inactivation (XCI), resulting in mosaic expression of one allele in each cell. Preferential inactivation of the paternal X chromosome is theorized to result in reduced disease severity; however, establishing such a correlation is complicated by known MECP2 genotype effects and an age-dependent increase in severity. To mitigate these confounding factors, we developed an age- and genotype-normalized measure of RTT severity by modeling longitudinal data collected in the US Rett Syndrome Natural History Study. This model accurately reflected individual increase in severity with age and preserved group-level genotype specific differences in severity, allowing for the creation of a normalized clinical severity score. Applying this normalized score to a RTT XCI dataset revealed that XCI influence on disease severity depends on MECP2 genotype with a correlation between XCI and severity observed only in individuals with MECP2 variants associated with increased clinical severity. This normalized measure of RTT severity provides the opportunity for future discovery of additional factors contributing to disease severity that may be masked by age and genotype effects. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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