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17 pages, 1471 KiB  
Article
RANKL/OPG Axis and Bone Mineral Density in Pediatric Inflammatory Bowel Disease
by Mariusz Olczyk, Agnieszka Frankowska, Marcin Tkaczyk, Anna Socha-Banasiak, Renata Stawerska, Anna Łupińska, Zuzanna Gaj, Ewa Głowacka and Elżbieta Czkwianianc
J. Clin. Med. 2025, 14(15), 5440; https://doi.org/10.3390/jcm14155440 (registering DOI) - 1 Aug 2025
Abstract
Background: Inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), may impair bone metabolism, particularly in children. The RANKL/OPG axis, as a key regulator of bone turnover, may contribute to these disturbances. However, data in the pediatric population [...] Read more.
Background: Inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), may impair bone metabolism, particularly in children. The RANKL/OPG axis, as a key regulator of bone turnover, may contribute to these disturbances. However, data in the pediatric population remain limited. Methods: A single-center, prospective observational study included 100 children aged 4–18 years, with a comparable number of girls and boys. Among them, 72 had IBD (27 CD, 45 UC) and 28 were healthy controls. Anthropometric, biochemical, and densitometric assessments were performed, including serum levels of RANKL and OPG, and markers of inflammation and bone turnover. Results: Children with CD had significantly lower height and weight percentiles compared to UC and controls. Serum RANKL and the RANKL/OPG ratio were significantly elevated in IBD patients, particularly in CD (p < 0.01). Total body BMD Z-scores were lower in IBD compared to controls (p = 0.03). Low BMD was found in 14.7% of UC and 26.3% of CD patients. In both groups, over 30% had values in the “gray zone” (−1.0 to −2.0). A positive correlation was observed between height and weight and bone density (p < 0.01). Higher OPG was associated with lower body weight (p < 0.001), while increased RANKL correlated with osteocalcin (p = 0.03). Patients receiving biological therapy had significantly lower BMD. Conclusions: Pediatric IBD is associated with significant alterations in the RANKL/OPG axis and reduced bone density. These findings support early screening and suggest RANKL/OPG as a potential biomarker of skeletal health. Full article
12 pages, 736 KiB  
Article
Visual Search Test for Residents Chronically Exposed to Methylmercury in the Minamata Area
by Shigeru Takaoka and Kenta Matsunaga
Toxics 2025, 13(8), 657; https://doi.org/10.3390/toxics13080657 (registering DOI) - 31 Jul 2025
Abstract
In individuals exposed to relatively mild methylmercury, even if they appeared to be independent in activities of daily living (ADL), slower judgment and motor responses in daily activities were observed, suggesting potential cognitive impairment. To quantitatively assess this impairment, we measured reaction time [...] Read more.
In individuals exposed to relatively mild methylmercury, even if they appeared to be independent in activities of daily living (ADL), slower judgment and motor responses in daily activities were observed, suggesting potential cognitive impairment. To quantitatively assess this impairment, we measured reaction time (RT) in a visual search test, as a visual cognitive ability test. The study participants included 24 residents from contaminated areas with sensory impairments in the limbs but no visual field defects (E group), as well as 12 individuals from non-contaminated areas (Group C). The 24 participants from contaminated areas were further divided into two groups: 12 without hand motor coordination disorders (Group E-HA) and 12 with such disorders (Group E+HA). Participants were instructed to search for the target letter “Z” on a computer screen, and the visual stimuli consisted of two, six, or ten alphabet letters. An equal number of trials contained “Z” and did not contain “Z,” for a total of thirty trials, which were conducted twice. RT was significantly longer in Group E+HA, followed by Group E-HA, and then Group C. However, in the second test, RT decreased in all cases, with a greater reduction in the exposed groups compared to the control group. These results suggest that methylmercury exposure may cause cognitive impairment, yet it also possesses plasticity. Full article
(This article belongs to the Special Issue Health Effects of Exposure to Environmental Pollutants—2nd Edition)
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13 pages, 256 KiB  
Article
Attempt to Quantify Molecules of Host Plant Volatiles Evoking an Electroantennographic Response in Anoplophora glabripennis Antennae
by Rui Zhang, Jian-Ming Shi, Yi-Bei Jiang, Hui-Quan Sun, Dan-Dan Cao, Hui-Ling Hao and Jian-Rong Wei
Insects 2025, 16(8), 781; https://doi.org/10.3390/insects16080781 - 30 Jul 2025
Viewed by 26
Abstract
Anoplophora glabripennis, is one of the most devastating wood borers of many broad leaf trees. Our previous results indicated that antennae of A. glabripennis showed electroantennogram (EAG) responses to several host plant volatiles. However, the quantities of active compounds necessary to trigger [...] Read more.
Anoplophora glabripennis, is one of the most devastating wood borers of many broad leaf trees. Our previous results indicated that antennae of A. glabripennis showed electroantennogram (EAG) responses to several host plant volatiles. However, the quantities of active compounds necessary to trigger an EAG response remains unclear. To relate EAG responses with quantities of active molecules, we quantified the level of molecular triggering in the EAG response of A. glabripennis by a series of procedures. First, we used the EAG apparatus to measure EAG responses of A. glabripennis to five concentrations of eight chemicals and obtained dose–response curves. Second, volatiles released after blowing air over filter paper loaded with volatiles for different numbers of times (purging) were collected by solid-phase microextraction (SPME) and quantified by gas chromatography (GC), so we obtained the quantity of chemical released from each purge; the minimum number of molecules in each purge in the EAG was calculated by the molar mass for different compounds. For instance, the number of molecules of (Z)-3-hexenol reaching the female antennal segment in EAG was 8.68 × 108 at 0.01 ng/μL concentration, and 1.39 × 105 at 0.01 mV potential value. Finally, by comparing sensilla numbers on tested antennal segments with the entire antennae, the minimum number of molecules, or molecular flow, of tested compounds required to elicit an electrophysiological response from two antennae of ALB could be estimated either at a minimum concentration (2.49 × 108 at 0.01 ng/μL concentration of (Z)-3-Hexenol, for female) or at a minimum potentiometric response value (3.99 × 104 at 0.01 mV potential value). Full article
(This article belongs to the Section Insect Pest and Vector Management)
12 pages, 317 KiB  
Article
Further Results on Bijective Product k-Cordial Labeling
by Sabah A. Bashammakh, Wai Chee Shiu, Robinson Santrin Sabibha, Pon Jeyanthi and Mohamed Elsayed Abdel-Aal
Mathematics 2025, 13(15), 2451; https://doi.org/10.3390/math13152451 - 30 Jul 2025
Viewed by 69
Abstract
A bijective product k-cordial labeling f of a graph G with vertex set V and edge set E is a bijection from V to {1,2,,|V|} such that the induced edge labeling [...] Read more.
A bijective product k-cordial labeling f of a graph G with vertex set V and edge set E is a bijection from V to {1,2,,|V|} such that the induced edge labeling f×:E(G)Zk={i|0ik1} defined as f×(uv)f(u)f(v)(modk) for every edge uvE satisfies the condition |ef×(i)ef×(j)|1, where i,jZk and ef×(i) is the number of edges labeled with i under f×. A graph which admits a bijective product k-cordial labeling is called a bijective product k-cordial graph. In this paper, we study bijective product π-cordiality for paths and cycles, where π is an odd prime. We determine bijective product π-cordiality for paths and cycles for 3π13. Also, we establish the bijective product k-cordial labeling of stars. Further, we find the bijective product 4-cordial labeling of bistars and the splitting graphs of stars and bistars. Full article
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30 pages, 435 KiB  
Article
Dombi Aggregation of Trapezoidal Neutrosophic Number for Charging Station Decision-Making
by Mohammed Alqahtani
Symmetry 2025, 17(8), 1195; https://doi.org/10.3390/sym17081195 - 26 Jul 2025
Viewed by 153
Abstract
In engineering and decision sciences, trapezoidal-valued neutrosophic fuzzy numbers (TzVNFNs) have become effective tools for managing imprecision and uncertainty in multi-attribute group decision-making (MAGDM) problems. This work introduces accumulation operators based on the Dombi t-norm [...] Read more.
In engineering and decision sciences, trapezoidal-valued neutrosophic fuzzy numbers (TzVNFNs) have become effective tools for managing imprecision and uncertainty in multi-attribute group decision-making (MAGDM) problems. This work introduces accumulation operators based on the Dombi t-norm (DTn) and Dombi t-conorm (DTcn) specifically designed for TzVNFNs. These operators enhance the flexibility, consistency, and fairness of the aggregation process. To demonstrate their practical applicability, we propose three novel geometric aggregation operator’s namely, the trapezoidal-valued neutrosophic fuzzy Dombi weighted geometric (TzVNFDWG), the trapezoidal-valued neutrosophic fuzzy Dombi ordered weighted geometric (TzVNFDOWG), and the trapezoidal-valued neutrosophic fuzzy Dombi hybrid Geometric (TzVNFDHG) operators. These are incorporated into a systematic MAGDM framework to support the selection of optimal locations for charging stations. Comparative analysis with current decision-making methodologies highlights the efficacy and benefits of the suggested method. The suggested method provides a flexible and mathematically based choice framework designed for uncertain condition. Full article
(This article belongs to the Section Mathematics)
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17 pages, 3481 KiB  
Article
Influence of Ziziphus lotus (Rhamnaceae) Plants on the Spatial Distribution of Soil Bacterial Communities in Semi-Arid Ecosystems
by Nabil Radouane, Zakaria Meliane, Khaoula Errafii, Khadija Ait Si Mhand, Salma Mouhib and Mohamed Hijri
Microorganisms 2025, 13(8), 1740; https://doi.org/10.3390/microorganisms13081740 - 25 Jul 2025
Viewed by 296
Abstract
Ziziphus lotus (L.) Lam. (Rhamnaceae), a key shrub species native to North Africa, is commonly found in arid and semi-arid regions. Renowned for its resilience under harsh conditions, it forms vegetation clusters that influence the surrounding environment. These clusters create microhabitats that promote [...] Read more.
Ziziphus lotus (L.) Lam. (Rhamnaceae), a key shrub species native to North Africa, is commonly found in arid and semi-arid regions. Renowned for its resilience under harsh conditions, it forms vegetation clusters that influence the surrounding environment. These clusters create microhabitats that promote biodiversity, reduce soil erosion, and improve soil fertility. However, in agricultural fields, Z. lotus is often regarded as an undesirable species. This study investigated the bacterial diversity and community composition along spatial gradients around Z. lotus patches in barley-planted and non-planted fields. Using 16S rRNA gene sequencing, 84 soil samples were analyzed from distances of 0, 3, and 6 m from Z. lotus patches. MiSeq sequencing generated 143,424 reads, representing 505 bacterial ASVs across 22 phyla. Alpha-diversity was highest at intermediate distances (3 m), while beta-diversity analyses revealed significant differences in community composition across distances (p = 0.035). Pseudomonadota dominated close to the shrub (44% at 0 m) but decreased at greater distances, whereas Bacillota and Actinobacteriota displayed distinct spatial patterns. A core microbiome comprising 44 ASVs (8.7%) was shared across all distances, with the greatest number of unique ASVs identified at 3 m. Random forest analysis highlighted Skermanella and Rubrobacter as key discriminatory taxa. These findings emphasize the spatial structuring of bacterial communities around Z. lotus patches, demonstrating the shrub’s substantial influence on bacterial dynamics in arid ecosystems. Full article
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10 pages, 395 KiB  
Article
Effect of the Coulomb Interaction on Nuclear Deformation and Drip Lines
by Kenta Hagihara, Takashi Nakatsukasa and Nobuo Hinohara
Particles 2025, 8(3), 72; https://doi.org/10.3390/particles8030072 - 24 Jul 2025
Viewed by 200
Abstract
Nuclei are self-bound systems in which the strong interaction (nuclear force) plays a dominant role, and the isospin is approximately a good quantum number. The isospin symmetry is primarily violated by electromagnetic interactions, namely Coulomb interactions among protons, the effects of which need [...] Read more.
Nuclei are self-bound systems in which the strong interaction (nuclear force) plays a dominant role, and the isospin is approximately a good quantum number. The isospin symmetry is primarily violated by electromagnetic interactions, namely Coulomb interactions among protons, the effects of which need be studied to understand the importance of the isospin symmetry. We investigate the effect of the Coulomb interaction on nuclear properties, especially quadrupole deformation and neutron drip line, utilizing the density functional method, which provides a universal description of nuclear systems in the entire nuclear chart. We carry out calculations of even–even nuclei with a proton number of 2Z60. The results show that the Coulomb interaction plays a significant role in enhancing quadrupole deformation across a wide range of nuclei. We also find that, after including the Coulomb interaction, some nuclei near the neutron drip line become stable against two-neutron emissions, resulting in a shift in the drip line towards larger neutron numbers. Full article
(This article belongs to the Section Nuclear and Hadronic Theory)
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24 pages, 31371 KiB  
Article
Ultrasound Phenotype-Based Approach to Treatment Choice in Osteoarthritis
by Rositsa Karalilova, Velichka Popova, Konstantin Batalov, Dimitar Kolev, Lyatif Kodzhaahmed, Dimitrina Petrova-Stoyankova, Nikola Tepeliev, Tsvetelina Kostova, Lili Mekenyan and Zguro Batalov
Life 2025, 15(7), 1140; https://doi.org/10.3390/life15071140 - 19 Jul 2025
Viewed by 304
Abstract
Introduction/Objectives: Osteoarthritis (OA) is a chronic systemic disease that affects the entire array of joint structures. It is one of the most common chronic, socially significant diseases, associated with a decline in the quality of life of patients and constantly increasing the cost [...] Read more.
Introduction/Objectives: Osteoarthritis (OA) is a chronic systemic disease that affects the entire array of joint structures. It is one of the most common chronic, socially significant diseases, associated with a decline in the quality of life of patients and constantly increasing the cost of treatment. Clinical trial outcomes are largely inconclusive, and OA remains one of the few musculoskeletal diseases without an established disease-modifying therapy. One potential explanation is the use of ineffective tools for OA classification, patient stratification, and the assessment of disease progression. There is growing interest in musculoskeletal ultrasonography (MSK US), as it enables the dynamic visualization of the examined structures and gives information about both inflammatory and structural changes that have occurred. Determining the leading ultrasound phenotype, which depends on the most damaged tissue at a given time (bone, cartilage, synovial membrane, joint capsule, ligaments, tendons, menisci, etc.), can rationalize therapy use by selecting patients more suitable for specific treatments. This article aims to evaluate and summarize the potential of MSK US in the process of determining the clinical phenotype of OA and to emphasize the importance of this imaging modality in evaluating further therapeutic strategies. Method: A single-center prospective study conducted in the period of September 2023–June 2024 enrolled 259 consecutive patients with proven OA. The statistical program Minitab version 22.2.1 (2025) was used to analyze the data. The predominant and secondary phenotypes were tabulated for each OA localization and were presented numerically and as relative proportions (%). The rate of the most frequently occurring phenotypes was compared against that of the less frequent ones through paired z-tests. The initially acceptable type I error was set at 5%; it was further adjusted for the number of comparisons (Bonferroni). Results: The most frequent and predominant US phenotype for patients with knee OA was intra-articular effusion (n = 47, 37.90%). It was significantly higher compared to the rest of the US phenotypes: synovial proliferation (n = 22, 17.70%; p < 0.001), cartilage destruction (n = 26, 21%; p = 0.001), altered subchondral bone (n = 8, 6.50%; p < 0.001), extra-articular soft tissue changes (n = 12, 9.70%; p < 0.001), crystal deposits (n = 6, 4.8%; p < 0.001), and post-traumatic (n = 3, 2.40%; p < 0.001). The most common US phenotype for hip OA was altered subchondral bone (n = 32, 47.1%), with significant differences from intra-articular effusion (n = 12, 17.60%; p = 0.001), synovial proliferation (n = 5, 7.40; p = 0.001), cartilage destruction (n = 12, 17.60%; p = 0.001), extra-articular soft tissue changes (n = 3, 4.40%; p = 0.001), crystal deposits (n = 3, 4.40%; p = 0.001), and post-traumatic (n = 0). Altered subchondral bone was also the leading US phenotype for hand OA (n = 31, 55.40%), with significant differences compared to intra-articular effusion (n = 1, 1.80%; p < 0.001), synovial proliferation (n = 7, 12.50%; p < 0.001), cartilage destruction (n = 11, 19.60%; p < 0.001), extra-articular soft tissue changes (n = 2, 3.60%; p < 0.001), crystal deposits (n = 3, 5.40%; p < 0.001), and post-traumatic (n = 1, 1.80%, p < 0.001). For shoulder OA, extra-articular soft tissue changes were the most frequent (n = 8, 46.20%), followed by post-traumatic (n = 4, 30.70%), as the rate of both phenotypes was significantly higher compared to that of intra-articular effusion (n = 0), synovial proliferation (n = 0), cartilage destruction (n = 1, 7.70%; p = 0.003), and crystal deposits (n = 0). Conclusions: The therapeutic approach for OA is a dynamic and intricate process, for which the type of affected joint and the underlying pathogenetic mechanism at a specific stage of the disease’s evolution is essential. MSK US is one of the options for the clinical phenotyping of OA. Some of the suggested ultrasound subtypes may serve as the rationale for selecting a particular treatment. Full article
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11 pages, 2975 KiB  
Article
Crystallographic Combinations: Understanding Polymorphism and Approximate Symmetry in N-(1,3-Thiazol-2-yl)benzamide
by Johannes C. Voigt, Michael J. Hall and Paul G. Waddell
Crystals 2025, 15(7), 657; https://doi.org/10.3390/cryst15070657 - 18 Jul 2025
Viewed by 381
Abstract
A new polymorph of N-(1,3-thiazol-2-yl)benzamide crystallises in the monoclinic space group Pc with four crystallographically independent molecules (Z′ = 4) in the asymmetric unit. Where the previously reported polymorphs exhibit two distinct hydrogen-bonded dimer geometries exclusively, the asymmetric unit of the new [...] Read more.
A new polymorph of N-(1,3-thiazol-2-yl)benzamide crystallises in the monoclinic space group Pc with four crystallographically independent molecules (Z′ = 4) in the asymmetric unit. Where the previously reported polymorphs exhibit two distinct hydrogen-bonded dimer geometries exclusively, the asymmetric unit of the new polymorph comprises both. Approximate symmetry was observed to relate the molecules of these dimers. These approximate symmetry elements combine to form a structure with distorted P21/c space group symmetry, rationalising the unexpectedly high number of crystallographically independent molecules. Full article
(This article belongs to the Special Issue Celebrating the 10th Anniversary of International Crystallography)
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11 pages, 255 KiB  
Article
New Sufficient Conditions for p-Valent Functions
by Mamoru Nunokawa, Janusz Sokół and Edyta Trybucka
Symmetry 2025, 17(7), 1141; https://doi.org/10.3390/sym17071141 - 16 Jul 2025
Viewed by 131
Abstract
A function that is holomorphic in a set E, in the complex plane, is called p-valent in E if, for every complex number, w, the equation f (z) = w has, at most, p roots in E. [...] Read more.
A function that is holomorphic in a set E, in the complex plane, is called p-valent in E if, for every complex number, w, the equation f (z) = w has, at most, p roots in E. In this paper, we established some sufficient conditions for holomorphic functions in the unit disk |z| < 1 to be at most p-valent in the unit disk or p-valent or p-valent starlike in the unit disk. Full article
(This article belongs to the Section Mathematics)
20 pages, 2542 KiB  
Article
How Benzoic Acid—Driven Soil Microorganisms Influence N2O Emissions
by Xinxing Zhang, Yinuo Zhao, Zhaoya Chen, Yelong Song, Wenhua Liao and Zhiling Gao
Agronomy 2025, 15(7), 1709; https://doi.org/10.3390/agronomy15071709 - 16 Jul 2025
Viewed by 487
Abstract
Urine-derived and plant-derived benzoic acid can accumulate within soil, and it likely changes the soil microbial community as well as N2O emissions; however, its mechanism is not clear. This study conducted an incubation experiment to monitor N2O emissions under [...] Read more.
Urine-derived and plant-derived benzoic acid can accumulate within soil, and it likely changes the soil microbial community as well as N2O emissions; however, its mechanism is not clear. This study conducted an incubation experiment to monitor N2O emissions under low moisture (40% water-filled pore space (WFPS)) and high moisture (85% WFPS) conditions. Metagenomic sequencing and q-PCR methods were used to determine the link between N2O emissions and the composition and functions of soil microbiota. Benzoic acid (BA) was found to significantly, yet dose-dependently, impact N2O emissions; that is, low BA concentrations increased N2O, whereas high BA decreased N2O. However, this was only found under high moisture conditions. In contrast, BA had little impact on N2O emissions under low moisture conditions. Under high moisture conditions, BA increased the gene copy number of bacteria and fungi, and decreased the ratio of bacteria to fungi. Similarly, BA significantly increased the abundance of denitrification functional genes, but reduced the (NirS + NirK)-to-NosZ ratio at the peak of emission. This is in agreement with the observation of the increased relative abundance of genes encoding N2O reductase (EC 1.7.2.4) and NO3 heterotrophic reductase (EC 1.7.1.15, EC 1.7.2.2) in the metagenomic analysis. In summary, high concentrations of benzoic acid reduce N2O emissions by promoting the reduction of N2O. This study revealed the impact of BA on soil microbiota and highlighted the favorable conditions and underlying mechanism behind BA’s significant impact on soil N2O emissions. This study’s novelty lies in the fact that it deepens our understanding of the complicated role of root exudates and metabolites of animals and plants in soil. Full article
(This article belongs to the Section Agroecology Innovation: Achieving System Resilience)
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17 pages, 6777 KiB  
Article
Filamentous Temperature-Sensitive Z Protein J175 Regulates Maize Chloroplasts’ and Amyloplasts’ Division and Development
by Huayang Lv, Xuewu He, Hongyu Zhang, Dianyuan Cai, Zeting Mou, Xuerui He, Yangping Li, Hanmei Liu, Yinghong Liu, Yufeng Hu, Zhiming Zhang, Yubi Huang and Junjie Zhang
Plants 2025, 14(14), 2198; https://doi.org/10.3390/plants14142198 - 16 Jul 2025
Viewed by 317
Abstract
Plastid division regulatory genes play a crucial role in the morphogenesis of chloroplasts and amyloplasts. Chloroplasts are the main sites for photosynthesis and metabolic reactions, while amyloplasts are the organelles responsible for forming and storing starch granules. The proper division of chloroplasts and [...] Read more.
Plastid division regulatory genes play a crucial role in the morphogenesis of chloroplasts and amyloplasts. Chloroplasts are the main sites for photosynthesis and metabolic reactions, while amyloplasts are the organelles responsible for forming and storing starch granules. The proper division of chloroplasts and amyloplasts is essential for plant growth and yield maintenance. Therefore, this study aimed to examine the J175 (FtsZ2-2) gene, cloned from an ethyl methanesulphonate (EMS) mutant involved in chloroplast and amyloplast division in maize, through map-based cloning. We found that J175 encodes a cell division protein, FtsZ (filamentous temperature-sensitive Z). The FtsZ family of proteins is widely distributed in plants and may be related to the division of chloroplasts and amyloplasts. The J175 protein is localized in plastids, and its gene is expressed across various tissues. From the seedling stage, the leaves of the j175 mutant exhibited white stripes, while the division of chloroplasts was inhibited, leading to a significant increase in volume and a reduction in their number. Measurement of the photosynthetic rate showed a significant decrease in the photosynthetic efficiency of j175. Additionally, the division of amyloplasts in j175 grains at different stages was impeded, resulting in irregular polygonal starch granules. RNA-seq analyses of leaves and kernels also showed that multiple genes affecting plastid division, such as FtsZ1, ARC3, ARC6, PDV1-1, PDV2, and MinE1, were significantly downregulated. This study demonstrates that the maize gene j175 is essential for maintaining the division of chloroplasts and amyloplasts and ensuring normal plant growth, and provides an important gene resource for the molecular breeding of maize. Full article
(This article belongs to the Special Issue Crop Genetics and Breeding)
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18 pages, 1297 KiB  
Article
Changing Etiological Spectrum of Premature Ovarian Insufficiency over the Past Decades: A Comparative Analysis of Two Cohorts from a Single Center
by Szilvia Csehely, Adrienn Kun, Edina Orbán, Tamás Katona, Mónika Orosz, Zoárd Tibor Krasznai, Tamás Deli and Attila Jakab
Diagnostics 2025, 15(13), 1724; https://doi.org/10.3390/diagnostics15131724 - 6 Jul 2025
Viewed by 527
Abstract
Background: Premature ovarian insufficiency (POI) is a complex and heterogeneous condition affecting women of reproductive age. Historically, most POI cases have been classified as idiopathic due to limited diagnostic capabilities. However, due to the success of oncologic treatments and the increasing number [...] Read more.
Background: Premature ovarian insufficiency (POI) is a complex and heterogeneous condition affecting women of reproductive age. Historically, most POI cases have been classified as idiopathic due to limited diagnostic capabilities. However, due to the success of oncologic treatments and the increasing number of gynecologic surgeries enabled by improved diagnostics, the proportion of iatrogenic POI cases has risen substantially. Objectives: To investigate the current prevalence of POI etiologies, to compare the etiological distribution between two POI cohorts from a single tertiary center—one historical (1978–2003) and one contemporary (2017–2024)—and to explore how the spectrum of underlying causes has changed over the past four decades. Methods: Data from 111 women diagnosed with POI between 2017 and 2024 were retrospectively reviewed and compared with those from a historical cohort of 172 patients. Etiologies were classified as genetic, autoimmune, iatrogenic, or idiopathic. Statistical comparisons were performed using chi-square and z-tests. Hormonal profiles and reproductive outcomes were also analyzed. Results: The current prevalence of POI etiologies is as follows: genetic 9.9%, autoimmune 18.9%, iatrogenic 34.2%, idiopathic 36.9%. In the historical POI cohort, etiologies were classified as genetic in 11.6%, autoimmune in 8.7%, iatrogenic in 7.6%, and idiopathic in 72.1%. The changes in the prevalence of autoimmune, iatrogenic, and idiopathic POI were statistically significant (p < 0.05). Reproductive outcomes remained limited: 10 pregnancies occurred in each cohort, with 7 live births in the contemporary group. Conclusions: Our findings suggest a significant shift in the etiological landscape of POI, with a notable, more than fourfold rise in identifiable iatrogenic cases and a twofold increase in the autoimmune group, resulting in a halving of idiopathic POI. Prevalence of genetic etiology remained unchanged. While diagnostic capabilities have improved, reproductive outcomes remain largely unchanged and suboptimal. Full article
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28 pages, 9146 KiB  
Review
Nanoscale Porphyrin-Based Metal–Organic Frameworks for Enhanced Radiotherapy–Radiodynamic Therapy: A Comprehensive Review
by Bin Gong, Qiuyun Zhang, Yijie Qu, Xiaohua Zheng and Weiqi Wang
Pharmaceutics 2025, 17(7), 883; https://doi.org/10.3390/pharmaceutics17070883 - 4 Jul 2025
Viewed by 520
Abstract
The phototherapeutic applications of porphyrin-based nanoscale metal–organic frameworks (nMOFs) are limited by the poor penetration of conventional excitation light sources into biological tissues. Radiodynamic therapy (RDT), which directly excites photosensitizers using X-rays, can overcome the issue of tissue penetration. However, RDT faces the [...] Read more.
The phototherapeutic applications of porphyrin-based nanoscale metal–organic frameworks (nMOFs) are limited by the poor penetration of conventional excitation light sources into biological tissues. Radiodynamic therapy (RDT), which directly excites photosensitizers using X-rays, can overcome the issue of tissue penetration. However, RDT faces the problems of low energy conversion efficiency, requiring a relatively high radiation dose, and the potential to cause damage to normal tissues. Researchers have found that by using some metals with high atomic numbers (high Z) as X-ray scintillators and coordinating them with porphyrin photosensitizers to form MOF materials, the excellent antitumor effect of radiotherapy (RT) and RDT can be achieved under low-dose X-ray irradiation, which can not only effectively avoid the penetration limitations of light excitation methods but also eliminate the defect issues associated with directly using X-rays to excite photosensitizers. This review summarizes the relevant research work in recent years, in which researchers have used metal ions with high Z, such as Hf4+, Th4+, Ta5+, and Bi3+, in coordination with carboxyl porphyrins to form MOF materials for combined RT and RDT toward various cancer cells. This review compares the therapeutic effects and advantages of using different high-Z metals and introduces the application of the heavy atom effect. Furthermore, it explores the introduction of a chemodynamic therapy (CDT) mechanism through iron coordination at the porphyrin center, along with optimization strategies such as oxygen delivery using hemoglobin to enhance the efficacy of these MOFs as radiosensitizers. This review also summarizes the potential of these materials in preclinical applications and highlights the current challenges they face. It is expected that the summary and prospects outlined in this review can further promote preclinical biomedical research into and the development of porphyrin-based nMOFs. Full article
(This article belongs to the Special Issue Advanced Nanotechnology for Combination Therapy and Diagnosis)
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20 pages, 7489 KiB  
Article
Insights into the Silver Camphorimine Complexes Interactions with DNA Based on Cyclic Voltammetry and Docking Studies
by Joana P. Costa, Gonçalo C. Justino, Fernanda Marques and M. Fernanda N. N. Carvalho
Molecules 2025, 30(13), 2817; https://doi.org/10.3390/molecules30132817 - 30 Jun 2025
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Abstract
Cyclic voltammetry (CV) is an accessible, readily available, non-expensive technique that can be used to search for the interaction of compounds with DNA and detect the strongest DNA-binding from a set of compounds, therefore allowing for the optimization of the number of cytotoxicity [...] Read more.
Cyclic voltammetry (CV) is an accessible, readily available, non-expensive technique that can be used to search for the interaction of compounds with DNA and detect the strongest DNA-binding from a set of compounds, therefore allowing for the optimization of the number of cytotoxicity assays. Focusing on this electrochemical approach, the study of twenty-seven camphorimine silver complexes of six different families was performed aiming at detecting interactions with calf thymus DNA (CT-DNA). All of the complexes display at least two cathodic waves attributed respectively to the Ag(I)→Ag(0) (higher potential) and ligand based (lower potential) reductions. In the presence of CT-DNA, a negative shift in the potential of the Ag(I)→Ag(0) reduction was observed in all cases. Additional changes in the potential of the waves, attributed to the ligand-based reduction, were also observed. The formation of a light grey product adherent to the Pt electrode in the case of {Ag(OH)} and {Ag2(µ-O)} complexes further corroborates the interaction of the complexes with CT-DNA detected by CV. The morphologic analysis of the light grey material was made by scanning electronic microscopy (SEM). The magnitude of the shift in the potential of the Ag(I)→Ag(0) reduction in the presence of CT-DNA differs among the families of the complexes. The complexes based on {Ag(NO3)} exhibit higher potential shifts than those based on {Ag(OH)}, while the characteristics of the ligand (AL-Y, BL-Y, CL-Z) and the imine substituents (Y,Z) fine-tune the potential shifts. The energy values calculated by docking corroborate the tendency in the magnitude of the interaction between the complexes and CT-DNA established by the reaction coefficient ratios (Q[Ag-DNA]/Q[Ag]). The molecular docking study extended the information regarding the type of interaction beyond the usual intercalation, groove binding, or electrostatic modes that are typically reported, allowing a finer understanding of the non-covalent interactions involved. The rationalization of the CV and cytotoxicity data for the Ag(I) camphorimine complexes support a direct relationship between the shifts in the potential and the cytotoxic activities of the complexes, aiding the decision on whether the cytotoxicity of a complex from a family is worthy of evaluation. Full article
(This article belongs to the Special Issue Metal-Based Drugs: Past, Present and Future, 3rd Edition)
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