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19 pages, 2301 KiB  
Article
Lactase Persistence-Associated rs4988235 Polymorphism: A Novel Genetic Link to Cardiovascular Risk via Modulation of ApoB100 and ApoAI
by Nihad Kharrat Helu, Habib Al Ashkar, Nora Kovacs, Roza Adany and Peter Piko
Nutrients 2025, 17(17), 2741; https://doi.org/10.3390/nu17172741 - 24 Aug 2025
Abstract
Background/Objectives: As part of the human adaptation to dairy consumption, the presence of the rs4988235-T variant in the MCM6 gene primarily determines lactase persistence in adult European populations, increasing the expression of the lactase-encoding LCT gene. Carriers of the C/C variant are [...] Read more.
Background/Objectives: As part of the human adaptation to dairy consumption, the presence of the rs4988235-T variant in the MCM6 gene primarily determines lactase persistence in adult European populations, increasing the expression of the lactase-encoding LCT gene. Carriers of the C/C variant are lactose intolerant, while carriers of the T/T or T/C variant have persistent lactase enzyme activity and are able to digest lactose in adulthood. While the association between lactose intolerance and increased cardiovascular risk (CVR) is well-known, the underlying causes have only been partly explored. The present study aimed to investigate the association of rs4988235 polymorphism with significant lipids affecting cardiovascular health and estimated CVR. Methods: The rs4988235 polymorphism was genotyped in 397 subjects from the general Hungarian population and 368 individuals from the Roma population. To characterize the overall lipid profile, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), apolipoprotein AI (ApoAI), and apolipoprotein B100 (ApoB100) levels were measured, and their ratios (TG/HDL-C, LDL-C/HDL-C, and ApoB100/ApoAI) were calculated. Cardiovascular risk was estimated using the Framingham Risk Score (FRS), Pooled Cohort Equations (PCE), Revised Pooled Cohort Equations (RPCE), and the Systematic Coronary Risk Evaluations (SCORE and SCORE2) algorithms. Adjusted linear and logistic regression analyses were performed, with p < 0.05 considered significant. Results: The Roma population had a significantly higher prevalence of the C/C genotype than the general population (65.5% vs. 40.3%, respectively). The results of the adjusted linear regression analysis showed a significant association between the C/C genotype and higher LDL-C level (B = 0.126, p = 0.047) and ApoB100 level (B = 0.046, p = 0.013), as well as a higher LDL-C/HDL-C ratio (B = 0.174, p = 0.021) and a higher ApoB100/ApoAI ratio (B = 0.045, p = 0.002), as well as a lower HDL-C level (B = −0.041, p = 0.049). The C/C genotype was also significantly associated with an increased cardiovascular risk (CVR) as estimated by the SCORE (B = 0.235, p = 0.034), SCORE2 (B = 0.414, p = 0.009), PCE (B = 0.536, p = 0.008), and RPCE (B = 0.289, p = 0.045) but not the FRS. After adjusting the statistical model further for ApoAI and ApoB100 levels, the significant correlation with the risk estimation algorithms disappeared (SCORE: p = 0.099; SCORE2: p = 0.283; PCE: p = 0.255; and RPCE: p = 0.370). Conclusions: Our results suggest that the C/C genotype of rs4988235 is associated with significantly higher ApoB100 and lower ApoAI levels and consequently higher ApoB100/ApoAI ratios, potentially contributing to an increased risk of cardiovascular disease. The results of the statistical analyses suggest that the association between lactose intolerant genotype and cardiovascular risk may be mediated indirectly via modification of the apolipoprotein profile. Full article
(This article belongs to the Special Issue Lipids and Lipoproteins in Cardiovascular Diseases)
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25 pages, 1030 KiB  
Article
Real-World Evidence of Neuropsychiatric Adverse Reactions to Isotretinoin: Insights from EudraVigilance (2005–2025)
by Denisa Viola Szilagyi, Delia Mirela Tit, Claudia Teodora Judea-Pusta, Andrei-Flavius Radu, Gabriela S. Bungau, Ada Radu, Laura Maria Endres and Ruxandra-Cristina Marin
Pharmaceuticals 2025, 18(9), 1252; https://doi.org/10.3390/ph18091252 - 24 Aug 2025
Abstract
Background/Objectives: Isotretinoin is a highly effective therapy for severe acne, but its potential neuropsychiatric adverse reactions (NPsRs) have been controversial. This study evaluated EudraVigilance data from 2005 to 2025 to better understand the frequency, typology, and predictors of such events. Methods: We conducted [...] Read more.
Background/Objectives: Isotretinoin is a highly effective therapy for severe acne, but its potential neuropsychiatric adverse reactions (NPsRs) have been controversial. This study evaluated EudraVigilance data from 2005 to 2025 to better understand the frequency, typology, and predictors of such events. Methods: We conducted a retrospective analysis of 33,381 individual case safety reports (ICSRs) related to isotretinoin. Using descriptive statistics, chi-square tests, and logistic regression, we assessed associations between NPsRs and variables such as age, sex, geographic region, and reporter type. Results: A total of 9793 cases (29.3%) involved at least one NPsR. Depression (31%) and suicidal ideation (8.6%) were the most frequently reported symptoms. Adolescents (12–17 years) had the highest proportion of NPsR cases, while male patients and reports submitted by non-healthcare professionals were significantly overrepresented. Reports from non-European Economic Area countries also had slightly increased odds of including NPsRs. All predictors were statistically significant in the logistic regression model, though the explained variance was modest (Nagelkerke R2 = 0.065). Conclusions: Neuropsychiatric reactions remain a prominent and persistent signal in isotretinoin pharmacovigilance, particularly among younger patients and non-professional reporters. Although causality cannot be inferred from spontaneous reporting data and confounding factors like acne-related depression cannot be excluded, these findings highlight the clinical value of pre-treatment psychiatric screening, patient-centered education, and proactive mental health monitoring throughout isotretinoin therapy. Full article
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37 pages, 900 KiB  
Review
Implicit Solvent Models and Their Applications in Biophysics
by Yusuf Bugra Severoglu, Betul Yuksel, Cagatay Sucu, Nese Aral, Vladimir N. Uversky and Orkid Coskuner-Weber
Biomolecules 2025, 15(9), 1218; https://doi.org/10.3390/biom15091218 - 23 Aug 2025
Abstract
:Solvents represent the quiet majority in biomolecular systems, yet modeling their influence with both speed and ri:gor remains a central challenge. This study maps the state of the art in implicit solvent theory and practice, spanning classical continuum electrostatics (PB/GB; DelPhi, APBS), [...] Read more.
:Solvents represent the quiet majority in biomolecular systems, yet modeling their influence with both speed and ri:gor remains a central challenge. This study maps the state of the art in implicit solvent theory and practice, spanning classical continuum electrostatics (PB/GB; DelPhi, APBS), modern nonpolar and cavity/dispersion treatments, and quantum–continuum models (PCM, COSMO/COSMO-RS, SMx/SMD). We highlight where these methods excel and where they falter, namely, around ion specificity, heterogeneous interfaces, entropic effects, and parameter sensitivity. We then spotlight two fast-moving frontiers that raise both accuracy and throughput: machine learning-augmented approaches that serve as PB-accurate surrogates, learn solvent-averaged potentials for MD, or supply residual corrections to GB/PB baselines, and quantum-centric workflows that couple continuum solvation methods, such as IEF-PCM, to sampling on real quantum hardware, pointing toward realistic solution-phase electronic structures at emerging scales. Applications across protein–ligand binding, nucleic acids, and intrinsically disordered proteins illustrate how implicit models enable rapid hypothesis testing, large design sweeps, and long-time sampling. Our perspective argues for hybridization as a best practice, meaning continuum cores refined by improved physics, such as multipolar water, ML correctors with uncertainty quantification and active learning, and quantum–continuum modules for chemically demanding steps. Full article
(This article belongs to the Special Issue Protein Biophysics)
13 pages, 258 KiB  
Article
Demographic and Premorbid Clinical Factors Predict Modified Rankin Score in Large and Medium Vessel Occlusion Ischemic Strokes
by Tara Srinivas, Dhairya A. Lakhani, Aneri B. Balar, Risheng Xu, Jee Moon, Caline Azzi, Nathan Hyson, Sijin Wen, Cynthia Greene, Janet Mei, Tyler McGaughey, Farzad Maroufi, Jeremy J. Heit, Tobias D. Faizy, Gregory W. Albers, Hamza Salim, Adam A. Dmytriw, Adrien Guenego, Meisam Hoseinyazdi and Vivek S. Yedavalli
J. Clin. Med. 2025, 14(17), 5960; https://doi.org/10.3390/jcm14175960 - 23 Aug 2025
Abstract
Background/Objectives: We report on the association of clinical, demographic, and peri- and intraoperative factors with patient outcomes in large- and, separately, medium-vessel acute ischemic stroke (AIS) occlusions treated with mechanical thrombectomy or medical thrombolysis. Increasingly, neuroimaging, particularly novel markers of collateral status, has [...] Read more.
Background/Objectives: We report on the association of clinical, demographic, and peri- and intraoperative factors with patient outcomes in large- and, separately, medium-vessel acute ischemic stroke (AIS) occlusions treated with mechanical thrombectomy or medical thrombolysis. Increasingly, neuroimaging, particularly novel markers of collateral status, has become useful in predicting response to endovascular treatment (EVT) among AIS patients. However, the relationship between these neuroimaging markers, documented predictors of stroke outcomes, and post-EVT functional status in anterior circulation large-vessel occlusions (LVOs) as compared to medium-vessel occlusions (MeVOs) remains unclear. We evaluated whether shared predictors of 90-day post-EVT functional outcomes in LVO compared to MeVO AIS patients within our institution exist. Methods: We retrospectively evaluated AIS patients treated at our institution between 9 January 2017 and 10 January 2023. The following were the inclusion criteria were applied: (i) CTA confirmed anterior circulation large or medium vessel occlusion; (ii) diagnostic CT perfusion was performed; (iii) mechanical thrombectomy was performed. A low modified Rankin score (mRS) indicating good functional outcomes (i.e., functional independence) was defined as less than or equal to 2, in accordance with prior studies. Univariate and multivariate logistic regression analyses were conducted to determine associations between demographic, clinical, and radiologic factors and mRS ≤ 2. Results: A total of 249 LVO (mean age 65.3 ± 16.2, 53.8% female) and 91 MeVO (mean age 68.9 ± 13.3, 46.2% female) patients met the inclusion criteria. Upon multivariate regression adjusted for race, age, hypertension, diabetes mellitus, radiologic features, IV alteplase, admission NIHSS, and reperfusion status, young age (p = 0.004), low admission NIHSS (p = 0.0001), and good reperfusion status (p = 0.007) were associated with good functional outcomes in LVO stroke. By contrast, no factors were significantly associated with good functional outcomes in MeVO stroke. Conclusions: Known factors, including young age, low admission stroke severity, and successful reperfusion predict EVT outcomes in LVO stroke but not necessarily in MeVO stroke. Further studies regarding predictors of MeVO outcomes in nonsurgical cases, including collateral status, may guide optimal medical management for this population. Full article
(This article belongs to the Special Issue Neurovascular Diseases: Clinical Advances and Challenges)
40 pages, 9864 KiB  
Article
Cascaded Hierarchical Attention with Adaptive Fusion for Visual Grounding in Remote Sensing
by Huming Zhu, Tianqi Gao, Zhixian Li, Zhipeng Chen, Qiuming Li, Kongmiao Miao, Biao Hou and Licheng Jiao
Remote Sens. 2025, 17(17), 2930; https://doi.org/10.3390/rs17172930 - 23 Aug 2025
Abstract
Visual grounding for remote sensing (RSVG) is the task of localizing the referred object in remote sensing (RS) images by parsing free-form language descriptions. However, RSVG faces the challenge of low detection accuracy due to unbalanced multi-scale grounding capabilities, where large objects have [...] Read more.
Visual grounding for remote sensing (RSVG) is the task of localizing the referred object in remote sensing (RS) images by parsing free-form language descriptions. However, RSVG faces the challenge of low detection accuracy due to unbalanced multi-scale grounding capabilities, where large objects have more prominent grounding accuracy than small objects. Based on Faster R-CNN, we propose Faster R-CNN in Visual Grounding for Remote Sensing (FR-RSVG), a two-stage method for grounding RS objects. Building on this foundation, to enhance the ability to ground multi-scale objects, we propose Faster R-CNN with Adaptive Vision-Language Fusion (FR-AVLF), which introduces a layered Adaptive Vision-Language Fusion (AVLF) module. Specifically, this method can adaptively fuse deep or shallow visual features according to the input text (e.g., location-related or object characteristic descriptions), thereby optimizing semantic feature representation and improving grounding accuracy for objects of different scales. Given that RSVG is essentially an expanded form of RS object detection, and considering the knowledge the model acquired in prior RS object detection tasks, we propose Faster R-CNN with Adaptive Vision-Language Fusion Pretrained (FR-AVLFPRE). To further enhance model performance, we propose Faster R-CNN with Cascaded Hierarchical Attention Grounding and Multi-Level Adaptive Vision-Language Fusion Pretrained (FR-CHAGAVLFPRE), which introduces a cascaded hierarchical attention grounding mechanism, employs a more advanced language encoder, and improves upon AVLF by proposing Multi-Level AVLF, significantly improving localization accuracy in complex scenarios. Extensive experiments on the DIOR-RSVG dataset demonstrate that our model surpasses most existing advanced models. To validate the generalization capability of our model, we conducted zero-shot inference experiments on shared categories between DIOR-RSVG and both Complex Description DIOR-RSVG (DIOR-RSVG-C) and OPT-RSVG datasets, achieving performance superior to most existing models. Full article
(This article belongs to the Section AI Remote Sensing)
16 pages, 1429 KiB  
Article
COSMO-RS Solubility Screening and Coumarin Extraction from Pterocaulon polystachyum with Deep Eutectic Solvents
by Victor Hugo Rodrigues, Arthur Cavassa, Júlia Cardeal, Nathalya Brazil, Helder Teixeira, Gilsane von Poser, Rubem Mário Vargas, Ana Rita Duarte and Eduardo Cassel
Molecules 2025, 30(17), 3468; https://doi.org/10.3390/molecules30173468 - 23 Aug 2025
Abstract
Deep eutectic solvents (DESs) have been studied to obtain extracts from medicinal plants, aiming for a more environmentally friendly process. Aligned with this initiative, the use of predictive thermodynamic models for screening the best solvent represents a theoretical action to reduce experimental time [...] Read more.
Deep eutectic solvents (DESs) have been studied to obtain extracts from medicinal plants, aiming for a more environmentally friendly process. Aligned with this initiative, the use of predictive thermodynamic models for screening the best solvent represents a theoretical action to reduce experimental time and cost. Therefore, this study aimed to perform and validate a relative solubility screening of 5-methoxy-6,7-methylenedioxycoumarin and prenyletin-methyl-ether at 313 K in choline chloride, menthol, and betaine-based DES, using the COSMO-RS model in COSMOThermX software. The density of DES was also predicted with a maximum error of 7.31% for this property. Ultrasound-assisted extraction (UAE) with DES at 313 K, 30 min, and a solid/liquid ratio of 1:20 (w/w) was performed to confirm the theoretical solubility results experimentally, as the extracts were analyzed through ultrafast liquid chromatography (UFLC) for coumarin content. For the results, the coumarin molecules presented intense peaks in the nonpolar region of their σ-profile, and the relative solubility screening indicated the DES Men/Lau (2:1), known for its hydrophobic nature and low polarity, as the best DES to solubilize these coumarins. Nevertheless, the UFLC results, and the complementary solubility screening of pigments, showed an interaction preference of this DES with chlorophylls instead of coumarins. This result was corroborated by spectrophotometric analysis of the extracts in UV-Vis, demonstrating that experimental validation is still mandatory in extraction processes and that predictive methodologies such as COSMO-RS should be used as guiding tools and analyzed in a greater context, considering the complexity of plant matrices in the beginning of simulations. Full article
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25 pages, 7172 KiB  
Article
Evaluation of Long-Term Skid Resistance in Granite Manufactured Sand Concrete
by Hongjie Li, Biao Shu, Chenglin Du, Yingming Zhuo, Zongxi Chen, Wentao Zhang, Xiaolong Yang, Yuanfeng Chen and Minqiang Pan
Lubricants 2025, 13(9), 375; https://doi.org/10.3390/lubricants13090375 - 23 Aug 2025
Abstract
The widespread application of granite manufactured sand (GS) concrete in pavement engineering is limited by issues such as suboptimal particle size distribution and an unclear optimal rock powder content. Furthermore, research on the long-term evolution of the skid resistance characteristics of GS concrete [...] Read more.
The widespread application of granite manufactured sand (GS) concrete in pavement engineering is limited by issues such as suboptimal particle size distribution and an unclear optimal rock powder content. Furthermore, research on the long-term evolution of the skid resistance characteristics of GS concrete remains relatively scarce. This knowledge gap makes it difficult to accurately assess the skid resistance performance of GS concrete in practical engineering applications, thereby compromising traffic safety. To address this research gap, this study utilized a self-developed indoor abrasion tester for pavement concrete to assess the skid resistance of GS concrete. Three-dimensional laser scanning was employed to acquire the concrete’s surface texture parameters. Using the friction coefficient and texture parameters as skid resistance evaluation indicators, and combining these with changes in the concrete’s surface morphology, the study explores how effective sand content, stone powder content, and fine aggregate lithology affect the long-term skid resistance of GS concrete pavements and reveals the evolution trends of their long-term skid resistance. Research results show that as the number of wear cycles increases, low and high effective sand content affect the surface friction coefficient of specimens in opposite ways. Specimens with 95% effective sand content exhibit superior skid resistance. Stone powder content influences the friction coefficient in three distinct variation patterns, showing no clear overall trend. Nevertheless, specimens with 5% stone powder content demonstrate better skid resistance. Among different fine aggregate lithologies, GS yields a higher friction coefficient than river sand (RS), while limestone manufactured sand (LS) shows significant friction coefficient fluctuations across different wear cycles. Adding stone powder substantially enhances mortar strength and delays groove collapse edge formation. Moreover, higher effective sand content and proper stone powder content mitigate bleeding, thereby improving mortar performance. Full article
(This article belongs to the Special Issue Tire/Road Interface and Road Surface Textures)
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14 pages, 1418 KiB  
Article
Evolution of Physiological Responses and Fatigue Analysis in Padel Matches According to Match Outcome and Playing Position
by Bingen Marcos-Rivero, Javier Yanci, Cristina Granados, Jon Mikel Picabea and Josu Ascondo
Sensors 2025, 25(17), 5240; https://doi.org/10.3390/s25175240 - 23 Aug 2025
Abstract
Padel is a doubles racket sport played on an enclosed court, characterised by intermittent high-intensity efforts, frequent directional changes, and short recovery periods. This study aimed to analyse the evolution of physiological responses and neuromuscular fatigue in amateur padel players according to playing [...] Read more.
Padel is a doubles racket sport played on an enclosed court, characterised by intermittent high-intensity efforts, frequent directional changes, and short recovery periods. This study aimed to analyse the evolution of physiological responses and neuromuscular fatigue in amateur padel players according to playing position (Right Side [RS] vs. Left Side [LS]) and match outcome (Win or Lose). A total of 52 padel players (35.6 ± 11.6 years) participated, competing in 13 matches. The mean match duration was 57.2 ± 15.7 min, with an average of 152.0 ± 40.4 points per match. Physiological variables were recorded during each set, and neuromuscular variables (countermovement jump [CMJ] and handgrip strength) were assessed before the match and after each set. No significant differences in physiological load were found between winners and losers or between RS and LS positions. However, differences in handgrip strength were observed at T1 (p < 0.05, d = −0.72) and T2 (p < 0.05, d = −0.59) (post-set testing), with LS players showing higher grip strength. Regarding the progression of physiological responses across the different sets, a progressive increase in cardiovascular load was observed within each subgroup, with significant differences across sets (set 1, set 2, and set 3) in several variables, including HRpeak, HRavg, zone 1, zone 2, zone 3, and TRIMPEdwards. No performance decline was observed in CMJ or handgrip strength in any of the groups analysed. These findings suggest that physiological responses increase throughout a match, particularly in the final sets, but no signs of neuromuscular fatigue (CMJ and handgrip) were observed, regardless of match outcome or playing position. These results highlight the need to include high-intensity scenarios and role-specific strategies in training to address the progressive physiological demands and positional differences in match play. Full article
(This article belongs to the Section Wearables)
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10 pages, 577 KiB  
Article
Placental Polycyclic Aromatic Hydrocarbon (PAH) Levels Are Associated with Spontaneous Preterm Birth
by Gwendolynn Hummel, Sohini Banerjee, Vasanta Putluri, Inaara Malick, Grace Johnson, Abu Hena Mostafa Kamal, Chandra Shekar R. Ambati, Nagireddy Putluri, Lori Showalter, Cynthia D. Shope, Joseph Hagan, Kjersti M. Aagaard, Bhagavatula Moorthy and Melissa A. Suter
Int. J. Mol. Sci. 2025, 26(17), 8179; https://doi.org/10.3390/ijms26178179 - 23 Aug 2025
Abstract
While the cause of preterm birth (PTB) (i.e., delivery before 37 weeks of gestation) is likely multifactorial, ambient exposure to environmental chemicals has been postulated to play a role in its etiology. Our prior studies of exposure to polycyclic aromatic hydrocarbons (PAHs) in [...] Read more.
While the cause of preterm birth (PTB) (i.e., delivery before 37 weeks of gestation) is likely multifactorial, ambient exposure to environmental chemicals has been postulated to play a role in its etiology. Our prior studies of exposure to polycyclic aromatic hydrocarbons (PAHs) in pregnancy have shown an increased level of placental PAH-induced bulky DNA adducts with increasing levels of PAH exposures. In this investigation, we hypothesized that higher levels of placental PAHs would be associated with an increased risk of PTB. Using gas chromatography and mass spectrometry (GC-MS/MS), we measured levels of benzo(a)pyrene (BaP), benzo(b)fluoranthene (BbF) and dibenz(a,h)anthracene (DBA) from n = 323 subjects. We found higher levels of BbF in placentae collected from preterm compared with term deliveries (mean 100.3 vs. 84.14 ng/mL, p = 0.038). Placental BbF levels negatively correlated with gestational age at delivery (rs = −0.171, p = 0.002) and placental DBA levels were higher in placentae from spontaneous PTBs compared to those that were medically indicated (mean 743.7 vs. 599.9 ng/mL, p = 0.049), suggesting a potentially causal role in spontaneous preterm birth. Lastly, we analyzed placental levels of each PAH in male (n = 164) and female (n = 159) gestations and found that levels of BaP are significantly higher in males (mean 204.4 vs. 169.9 ng/mL, p = 0.049). These studies show a potential causal role of PAH exposure in the etiology of spontaneous preterm birth. Full article
(This article belongs to the Collection New Advances in Molecular Toxicology)
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17 pages, 1537 KiB  
Article
Genome-Wide Association Study of Osteoporosis Risk in Korean Pre-Menopausal Women: The Korean Genome and Epidemiology Study
by Su Kang Kim, Seoung-Jin Hong, Gyutae Kim, Ju Yeon Ban and Sang Wook Kang
Int. J. Mol. Sci. 2025, 26(17), 8177; https://doi.org/10.3390/ijms26178177 - 22 Aug 2025
Abstract
Osteoporosis is a common disease characterized by a reduction in bone mineral density (BMD), leading to an increased risk of pathological fractures and even mortality. Although menopause is a major risk factor, osteoporosis can also occur in premenopausal women. The aim of this [...] Read more.
Osteoporosis is a common disease characterized by a reduction in bone mineral density (BMD), leading to an increased risk of pathological fractures and even mortality. Although menopause is a major risk factor, osteoporosis can also occur in premenopausal women. The aim of this study was to identify genetic variants associated with the development of osteoporosis in Korean premenopausal women. Subjects were recruited from the Anseong and Ansan cohorts of the Korean Genome and Epidemiology Study (KoGES). Clinical and epidemiological characteristics were assessed, and participants were classified based on BMD values measured at the distal radius and mid-shaft tibia. Individuals with confounding risk factors such as low body weight, smoking, high alcohol consumption, steroid/hormone therapy, or relevant medical history were excluded. A total of 247 healthy controls and 57 osteoporosis patients were included. Genotyping was performed using the Illumina Infinium HumanExome BeadChip and the Affymetrix Axiom Exome Array. Data were analyzed using the SNP and Variation Suite and PLINK, with quality control thresholds set at MAF ≥ 0.05 and HWE p ≥ 0.01. Functional annotation and protein structure predictions were performed using PolyPhen-2, SIFT, and PROVEAN. Genome-wide association analyses identified 113 single-nucleotide polymorphisms (SNPs) in 69 genes significantly associated with osteoporosis (p < 0.05) in both platforms, with 18 SNPs showing high cross-platform consistency (p < 0.01). Several of these genes were implicated in bone metabolism (e.g., ESRRG, PECAM1, COL6A5), vitamin D metabolism (e.g., NADSYN1, EFTUD1), skeletal muscle function (e.g., PACSIN2, ESRRG), and reproductive processes (e.g., CPEB1, EFCAB6, ASXL3). Notably, the CPEB1 rs783540 SNP exhibited the strongest association (p < 0.001) in both analyses. Our findings suggest that genetic polymorphisms in pathways related to bone metabolism, vitamin D signaling, muscle–bone interaction, and reproductive hormone regulation may contribute to the development of osteoporosis in Korean premenopausal women. These results provide a genetic basis for early identification of at-risk individuals and warrant further functional studies to elucidate the underlying mechanisms. Full article
(This article belongs to the Special Issue Molecular Biology of Osteoporosis)
15 pages, 6970 KiB  
Article
Regulatory Characterization of Two Cop Systems for Copper Resistance in Pseudomonas putida
by Huizhong Liu, Yafeng Song, Ping Yang, Qian Wang, Ping Huang, Zhiqing Zhang, Gang Zhou, Qingshan Shi and Xiaobao Xie
Int. J. Mol. Sci. 2025, 26(17), 8172; https://doi.org/10.3390/ijms26178172 - 22 Aug 2025
Abstract
Copper ions serve as essential cofactors for many enzymes but exhibit toxicity at elevated concentrations. In Gram-negative bacteria, the Cop system, typically encoded by copABCD, plays a crucial role in maintaining copper homeostasis and detoxification. The chromosome of Pseudomonas putida harbors two [...] Read more.
Copper ions serve as essential cofactors for many enzymes but exhibit toxicity at elevated concentrations. In Gram-negative bacteria, the Cop system, typically encoded by copABCD, plays a crucial role in maintaining copper homeostasis and detoxification. The chromosome of Pseudomonas putida harbors two copAB clusters but lacks copCD, along with two copR-copS clusters that encode the cognate two-component system. Here, the roles of these Cop components in countering copper toxicity were studied. We found that copAB2 was essential for full resistance to Cu2+ in P. putida, while copAB1 made only a minor contribution, partially due to its low expression. The two-component systems CopRS1 and CopRS2 both played significant regulatory roles in copper resistance. Although they could compensate for the absence of each other to mediate copper resistance, they exhibited distinct regulatory effects. CopR1 bound to all four cop promoters and activated their transcription under copper stress. In contrast, though CopR2 bound to the same sites as CopR1 in each cop promoter, it significantly activated only copAB2 and copRS2 expression. Its competitive binding at the copAB1 and copRS1 promoters likely impeded CopR1-mediated activation of these genes. Overall, this study reveals the distinct contributions of the two Cop systems to copper resistance and their regulatory interplay in P. putida. Full article
(This article belongs to the Section Molecular Biology)
13 pages, 2256 KiB  
Article
The Influence of the Ar/N2 Ratio During Reactive Magnetron Sputtering of TiN Electrodes on the Resistive Switching Behavior of MIM Devices
by Piotr Jeżak, Aleksandra Seweryn, Marcin Klepka and Robert Mroczyński
Materials 2025, 18(17), 3940; https://doi.org/10.3390/ma18173940 - 22 Aug 2025
Abstract
Resistive switching (RS) phenomena are nowadays one of the most studied topics in the area of microelectronics. It can be observed in Metal–Insulator–Metal (MIM) structures that are the basis of resistive switching random-access memories (RRAMs). In the case of commercial use of RRAMs, [...] Read more.
Resistive switching (RS) phenomena are nowadays one of the most studied topics in the area of microelectronics. It can be observed in Metal–Insulator–Metal (MIM) structures that are the basis of resistive switching random-access memories (RRAMs). In the case of commercial use of RRAMs, it is beneficial that the applied materials would have to be compatible with Complementary Metal-Oxide-Semiconductor (CMOS) technology. Fabricating methods of these materials can determine their stoichiometry and structural composition, which can have a detrimental impact on the electrical performance of manufactured devices. In this study, we present the influence of the Ar/N2 ratio during reactive magnetron sputtering of titanium nitride (TiN) electrodes on the resistive switching behavior of MIM devices. We used silicon oxide (SiOx) as a dielectric layer, which was characterized by the same properties in all fabricated MIM structures. The composition of TiN thin layers was controlled by tuning the Ar/N2 ratio during the deposition process. The fabricated conductive materials were characterized in terms of chemical and structural properties employing X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) analysis. Structural characterization revealed that increasing the Ar content during the reactive sputtering process affects the crystallite size of the deposited TiN layer. The resulting crystallite sizes ranged from 8 Å to 757.4 Å. The I-V measurements of fabricated devices revealed that tuning the Ar/N2 ratio during the deposition of TiN electrodes affects the RS behavior. Our work shows the importance of controlling the stoichiometry and structural parameters of electrodes on resistive switching phenomena. Full article
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14 pages, 649 KiB  
Article
Polygenic Risk Score Associated with Gestational Diabetes Mellitus in an AmericanIndian Population
by Karrah Peterson, Camille E. Powe, Quan Sun, Crystal Azure, Tia Azure, Hailey Davis, Kennedy Gourneau, Shyanna LaRocque, Craig Poitra, Sabra Poitra, Shayden Standish, Tyler J. Parisien, Kelsey J. Morin and Lyle G. Best
J. Pers. Med. 2025, 15(9), 395; https://doi.org/10.3390/jpm15090395 - 22 Aug 2025
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Abstract
Background/Objectives: Gestational diabetes mellitus (GDM) is a state of hyperglycemia during pregnancy, increasing the risk of birth complications, and subsequent type 2 diabetes mellitus in the mother and offspring. Risk factors such as diet, obesity, and family history have demonstrated strong association with [...] Read more.
Background/Objectives: Gestational diabetes mellitus (GDM) is a state of hyperglycemia during pregnancy, increasing the risk of birth complications, and subsequent type 2 diabetes mellitus in the mother and offspring. Risk factors such as diet, obesity, and family history have demonstrated strong association with GDM, but no clear pathophysiology has been ascertained. Methods: An analysis was conducted on 38 women with and 296 without GDM, within a case/control study of pre-eclampsia. The genetic variants examined were selected from among a published polygenic risk score of 10 variants (PRS-10). Genetic models were evaluated for each variant by multivariate logistic regression methods adjusted for age, body mass index, and pre-eclampsia. Since the genotypes for three of the PRS-10 were not available, a risk score comprising the total risk alleles among seven of the variants (PRS-7) was evaluated among those with all genotypes available. Results: Multivariate logistic regression showed significant, independent, positive associations between body mass index (BMI) and age. The posited PRS-7 showed a trend (OR 1.56, 95% CI 0.92–2.56, p = 0.070), and sensitivity analysis comprising three variants (PRS-3) was significantly associated with GDM (OR 2.43, 95% CI 1.17–5.06, p = 0.017). In univariate analysis, rs1421085 was associated with GDM (OR 0.50, 95% CI 0.26–0.95, p = 0.034), but not after adjustment for covariates, and paradoxically not for the expected risk allele. None of the other six variants showed an individual association with GDM. The previously published meta-analysis of PRS-10 showed a degree of heterogeneity (pQ= 0.03) among the three cohorts analyzed, suggesting that variant effects may differ according to the genetic background, which points to the importance of examining the generalizability of any posited polygenic risk scores. Conclusions: In conclusion, we provide additional support for and further refine the results of a previously published polygenic risk score for GDM in an ethically unrelated population. Full article
(This article belongs to the Section Omics/Informatics)
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12 pages, 965 KiB  
Article
Clinical Characteristics and Survival of Patients with Idiopathic Pulmonary Fibrosis: Analysis of the Serbian Cohort from the EMPIRE Registry
by Sanja Dimic-Janjic, Mihailo Stjepanovic, Slobodan Belic, Dragan Vukosavljevic, Ivan Milivojevic, Nikola Trboljevac, Nikola Nikolic, Slavko Stamenic, Maja Stojanovic, Kristina Stosic, Martina Koziar Vasakova, Ruza Stevic, Nikola Colic, Katarina Lukic, Miroslav Ilic, Lidija Isovic, Nikola Maric, Spasoje Popevic, Violeta Vucinic-Mihailović, Svetlana Kasikovic Lecic, Slavica Mojsilovic, Tatjana Pejcic, Dragana Jovanovic and the Serbian EMPIRE Investigatorsadd Show full author list remove Hide full author list
Diagnostics 2025, 15(17), 2121; https://doi.org/10.3390/diagnostics15172121 - 22 Aug 2025
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Abstract
Background/Objectives: Idiopathic pulmonary fibrosis (IPF) registries are established to enhance understanding of its natural history. Methods: Serbia (RS) participated in the EMPIRE (European Multi-Partner IPF Registry) from June 2015 to October 2022, involving four centers. The registry included patients over 18 [...] Read more.
Background/Objectives: Idiopathic pulmonary fibrosis (IPF) registries are established to enhance understanding of its natural history. Methods: Serbia (RS) participated in the EMPIRE (European Multi-Partner IPF Registry) from June 2015 to October 2022, involving four centers. The registry included patients over 18 diagnosed with IPF based on the 2011 international criteria. We aimed to gather key clinical, functional, and survival data, along with treatment information for IPF patients in RS, using a centralized electronic case report for consistency. Results: 188 RS patients participated (median age at diagnosis 65, 63.8% male, 51% smoking history, 56% radiological usual interstitial pneumonia (UIP) pattern). At the diagnosis, median forced vital capacity (FVC) was 73.7% and diffusion capacity for carbon monoxide (DLCO) was 38%. At initiation of antifibrotic therapy, median FVC was 73.2% (71.5% for deceased, 75.8% for survivors (p = 0.455), and DLCO was 33.8% (19.9% for deceased, and 35.6% for survivors (p = 0.046)). The median long-term survival from diagnosis was 29.4 months (95% CI: 22.6–36.2 months), and 9.4 months (95% CI: 5.9–12.9 months) from the initiation of therapy, with no difference in the duration of antifibrotic treatment between survivors and deceased (p = 0.598). Conclusions: The RS EMPIRE cohort represents a younger, less comorbid population with fewer smokers and more probable UIP, factors linked to a favorable prognosis. Nevertheless, survival was poorer than expected, mainly due to advanced disease severity at the time of antifibrotic initiation, as indicated by lower DLCO. These findings highlight the importance of earlier diagnosis and treatment before significant physiological decline to improve outcomes. Full article
(This article belongs to the Special Issue Respiratory Diseases: Diagnosis and Management)
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18 pages, 9714 KiB  
Article
Research on Physicochemical Properties and In Vitro Digestive Characteristics of High-Amylose Corn Starch–Ultrasound-Treated Waxy Rice Flour Blends
by Yuxing Wang, Yu Guo, Zhiting Zhu, Yan Ding, Yuchan Yang, Dongxu Wang, Zhanming Li, Yuanxin Guo and Xiaoman Chen
Foods 2025, 14(16), 2920; https://doi.org/10.3390/foods14162920 - 21 Aug 2025
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Abstract
This study aimed to investigate the effect of high-amylose corn starch (HACS) addition on the physicochemical properties and in vitro digestibility of an ultrasound-treated waxy rice flour (UWRF)–HACS blend system. As the proportion of HACS increased, the amylose content in the blends significantly [...] Read more.
This study aimed to investigate the effect of high-amylose corn starch (HACS) addition on the physicochemical properties and in vitro digestibility of an ultrasound-treated waxy rice flour (UWRF)–HACS blend system. As the proportion of HACS increased, the amylose content in the blends significantly increased (p < 0.05), while their water solubility index (WSI) and swelling power (SP) significantly decreased (p < 0.05). Additionally, the average particle size of the blends increased, and the surface of starch granules became smoother. Compared to UWRF, the blends did not generate new functional groups, but increased the starch’s relative crystallinity and short-range ordered structure. Rheological results indicated that the HACS-UWRF blends were mainly elastic and exhibited a typical weak gel system. In vitro digestibility results showed that the addition of HACS significantly increased the resistant starch (RS) content in the rice cakes (p < 0.05), while substantially reducing the hydrolysis index (HI) and estimated glycemic index (eGI) (p < 0.05). This study revealed the processing characteristics and gelatinization behavior changes in the HACS-UWRF blends. It provides a theoretical basis for the development of specialized flour for slow-glycemic rice cakes. Full article
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