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Keywords = repeat instability

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16 pages, 3803 KB  
Article
Evaluation of Biocompatible and Biodegradable PES/PCL Membranes for Potential Use in Biomedical Devices: From Fouling Resistance to Environmental Safety
by Cezary Wojciechowski, Monika Wasyłeczko, Dorota Lewińska and Andrzej Chwojnowski
Molecules 2025, 30(19), 3887; https://doi.org/10.3390/molecules30193887 - 25 Sep 2025
Abstract
The paper presents a method for obtaining partially degradable capillary membranes from a polyethersulfone/polycaprolactone (PES/PCL) mixture. PES/PCL membranes were obtained by the phase inversion technique with dry/wet spinning and then subjected to controlled degradation in an alkaline environment (1 M NaOH) and simulated [...] Read more.
The paper presents a method for obtaining partially degradable capillary membranes from a polyethersulfone/polycaprolactone (PES/PCL) mixture. PES/PCL membranes were obtained by the phase inversion technique with dry/wet spinning and then subjected to controlled degradation in an alkaline environment (1 M NaOH) and simulated body fluid (SBF with pH 7.4) using the flow method. The aim of the work was to select and apply a degradable, non-toxic, simple polymer as a removable component of the membrane structure. The degradable component of the membranes was PCL, the gradual hydrolysis of which was aimed at increasing the porosity and improving the transport properties of the membranes during operation. The membrane properties, such as hydraulic permeability coefficient (UFC), retention coefficient, and structural morphology, were assessed using scanning electron microscopy (SEM) before and after degradation. Analysis of SEM images performed with MeMoExplorerTM software showed an increase in the proportion of large pores (above 300 µm2) and total porosity of the membranes after degradation in NaOH and SBF. Low instability factor (<0.25) for all samples, both before and after degradation, confirms the good repeatability of the membrane structure. An increase in the UFC was observed, while the retention coefficients did not change significantly in the case of membranes after the etching process. The degradation of the PCL component in the membrane was assessed using the weight method. Measurements of the membrane mass loss before and after degradation confirmed the removal of over 50 wt.% of the PCL component in SBF and 70 wt.% in NaOH from the tested membranes, which resulted in an increase in permeability due to increased membrane porosity. The results indicate the possibility of using such structures as functional, partially self-regulating membranes, potentially useful in biomedical and environmental applications. Full article
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14 pages, 1584 KB  
Article
Starvation During the Larval Stage Driving Population Decline in the Butterfly Specialist Luehdorfia chinensis Leech, 1893 (Lepidoptera: Papilionidae)
by Wenjing Yang, Qi Zhu, Yunhao Zou, Chao Yang, Wenguo Wu, Qin Zou and Juping Zeng
Insects 2025, 16(10), 995; https://doi.org/10.3390/insects16100995 - 24 Sep 2025
Viewed by 57
Abstract
Host plant limitation poses a major threat to the endangered specialist butterfly Luehdorfia chinensis Leech, 1893, whose larvae are oligophagous at the species level on Asarum spp., while local populations often appear monophagous, depending on the host plants (A. sieboldii Miq. or [...] Read more.
Host plant limitation poses a major threat to the endangered specialist butterfly Luehdorfia chinensis Leech, 1893, whose larvae are oligophagous at the species level on Asarum spp., while local populations often appear monophagous, depending on the host plants (A. sieboldii Miq. or A. forbesii Maxim.) available in their habitat. To simulate natural starvation caused by host plant scarcity, third- to fifth-instar larvae were subjected to a three-day deprivation treatment, and the effects on individual fitness traits—including larval development, pupal duration, and adult fecundity—were assessed, along with population dynamics. Starvation significantly prolonged larval development, shortened the pupal stage, reduced female fecundity, and markedly decreased key population parameters, such as the intrinsic rate of increase (rm) and the net reproductive rate (R0). Population projections further indicated that repeated starvation stress could reduce population size by more than 83% within two years, potentially intensifying genetic drift, inbreeding depression, and demographic instability, ultimately increasing the risk of extinction. These findings provide direct evidence that host plant limitation drives population decline in L. chinensis, contribute to the broader understanding of global butterfly declines, and underscore the critical importance of conserving and restoring essential habitat resources. Moreover, they highlight the relevance of the resource-based habitat concept for the effective protection of specialist species. Full article
(This article belongs to the Special Issue Lepidoptera: Behavior, Ecology, and Biology)
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11 pages, 3371 KB  
Case Report
A Relapsed AML Case Featuring MYC and MECOM Rearrangements
by Kevin A. Murgas, Pons Materum, Luke Z. Li, Jacob Rocha, Michael Schuster, Tahmeena Ahmed and Carlos A. Tirado
Diagnostics 2025, 15(18), 2410; https://doi.org/10.3390/diagnostics15182410 - 22 Sep 2025
Viewed by 182
Abstract
Background/Objectives: Relapsed acute myeloid leukemia (AML) is often characterized by clonal evolution and acquired genomic abnormalities, which can inform prognosis and direct therapeutic decisions. The emergence of high-risk chromosomal rearrangements during relapse is of particular significance, yet the impact of rare and complex [...] Read more.
Background/Objectives: Relapsed acute myeloid leukemia (AML) is often characterized by clonal evolution and acquired genomic abnormalities, which can inform prognosis and direct therapeutic decisions. The emergence of high-risk chromosomal rearrangements during relapse is of particular significance, yet the impact of rare and complex events remains poorly understood. This report details a case of relapsed AML that demonstrated rare MYC and MECOM rearrangements and additional features that were not observed at initial diagnosis, emphasizing the clinical relevance of serial cytogenetic assessments. Case Description: A 70-year-old man was initially diagnosed with AML, exhibiting monocytic differentiation, an 11q23 deletion involving KMT2A loss, and a U2AF1 mutation. After achieving remission with azacitidine and venetoclax, the patient relapsed within ten months, necessitating reevaluation and modification of therapy. Repeat cytogenetic analysis at relapse revealed a distinct t(3;8)(q26.2;q24.3) exhibiting MYC and MECOM rearrangements, features that were absent at initial diagnosis. Conclusions: This case underscores the importance of serial cytogenetic and molecular profiling in relapsed AML. The emergence of new abnormalities upon relapse suggested underlying genomic instability and clonal evolution. MYC rearrangements are notably rare in AML, especially with concurrent MECOM rearrangements, highlighting a unique feature of this case. The identification of novel abnormalities at relapse may carry prognostic and therapeutic significance and may be used to refine risk stratification. Thus, ongoing cytogenetic monitoring is essential to adapt management approaches in evolving disease contexts. Full article
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10 pages, 1094 KB  
Article
Clinical Outcomes of Radial Collateral Ligament Repair in Recalcitrant Lateral Epicondylitis with Mild Elbow Instability Following Repeated Steroid Injections
by Sang Won Moon, Darryl D’Lima and Jin-Young Bang
J. Clin. Med. 2025, 14(18), 6474; https://doi.org/10.3390/jcm14186474 - 14 Sep 2025
Viewed by 225
Abstract
Background: Lateral epicondylitis is a common degenerative condition of the elbow, often managed conservatively. However, a subset of patients who had recalcitrant symptoms and repeated corticosteroid injections may develop subtle lateral elbow instability, particularly involving the radial collateral ligament (RCL). This study aimed [...] Read more.
Background: Lateral epicondylitis is a common degenerative condition of the elbow, often managed conservatively. However, a subset of patients who had recalcitrant symptoms and repeated corticosteroid injections may develop subtle lateral elbow instability, particularly involving the radial collateral ligament (RCL). This study aimed to evaluate the clinical outcomes of RCL repair combined with open ECRB debridement in patients with chronic lateral epicondylitis and mild instability. Methods: We retrospectively reviewed 92 patients who underwent surgery for recalcitrant lateral epicondylitis between 2016 and 2022. Twelve patients with imaging and intraoperative findings of mild lateral instability underwent open RCL repair with or without LUCL augmentation (unstable group). The remaining 80 patients without instability underwent arthroscopic ECRB release and drilling (stable group). Pre- and postoperative outcomes were assessed using VAS, MEPS, DASH, and range of motion. Comparative analyses were performed between the two groups. Results: All unstable patients had a history of repeated steroid injections (mean 3.4) for 18 months. Postoperatively, pain scores (VAS) improved from 6.8 to 1.4, MEPS increased from 53 to 91, and DASH decreased from 47.1 to 13.8. No major complications or recurrent instability were observed at one-year follow-up. Subgroup analysis revealed that older age, previous surgery, and a greater number of injections were significantly associated with instability. Conclusions: RCL repair combined with ECRB debridement yields favorable clinical outcomes in patients with recalcitrant lateral epicondylitis and mild instability, especially those who had a history of repeated corticosteroid injections. Proper evaluation and surgical repair of underlying ligament pathology may improve outcomes in this subset of patients. Favorable clinical outcomes were defined as improvements compared to preoperative baseline scores. These outcomes were compared to preoperative scores and exceeded MCID thresholds where applicable. Full article
(This article belongs to the Section Orthopedics)
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16 pages, 2790 KB  
Article
Mechanism Insights in Freeze–Thaw Process Impacting Cold Denaturation of Gluten Proteins During Frozen Storage
by Yang Li, Yilin Sun, Shuya Chen, Mingfei Li, Xiaowei Zhang and Yujie Lu
Foods 2025, 14(17), 3103; https://doi.org/10.3390/foods14173103 - 5 Sep 2025
Viewed by 622
Abstract
Cold denaturation of gluten proteins during prolonged frozen storage or repeated freeze–thaw cycles can severely affect the quality of frozen cereal products. While both processes have been studied individually, their combined effects and underlying mechanisms remain unclear. This study systematically evaluated the hydration [...] Read more.
Cold denaturation of gluten proteins during prolonged frozen storage or repeated freeze–thaw cycles can severely affect the quality of frozen cereal products. While both processes have been studied individually, their combined effects and underlying mechanisms remain unclear. This study systematically evaluated the hydration properties and conformational changes in gluten proteins stored at −73 °C and −23 °C, with or without freeze–thaw cycling. Compared to continuous storage, freeze–thaw cycles reduced water-holding capacity by 9.1–12.2% and increased oil-holding capacity by 5.3–10.3%, indicating aggravated structural damage. Ultra-low temperature storage (−73 °C) suppressed ice crystal growth, preserved hydration, and limited hydrophobic residue exposure. Spectroscopic analyses revealed a temperature-dependent shift from α-helices to β-sheets and β-turns, which was accelerated by freeze–thaw cycles. Enhanced hydrophobic interactions and tryptophan exposure further indicated destabilization. Molecular dynamics simulations showed that increased hydrogen bonding between proteins and water contributed to unfolding at low temperatures, while temperature fluctuations intensified denaturation through repeated hydrogen bond breakage and reformation. These results underscore the critical role of thermal instability in cold denaturation and offer mechanistic insights for improving cryoprotection strategies in frozen food systems. Full article
(This article belongs to the Section Grain)
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18 pages, 3126 KB  
Article
The In Vitro Toxicity Profile of Nanoencapsulated Curcumin in a Chitosan–Alginate Gel Carrier Using Rabbit Lymphocytes: Preliminary Research
by Marta Kuchta-Gładysz, Joanna Wojciechowska-Puchałka, Anna Grzesiakowska-Dul, Michał Kmiecik, Karen Khachatryan and Gohar Khachatryan
Int. J. Mol. Sci. 2025, 26(17), 8577; https://doi.org/10.3390/ijms26178577 - 3 Sep 2025
Viewed by 437
Abstract
Curcumin is a natural bioactive compound of plant origin, characterised by a wide variety of properties that make it useful in numerous industries. Furthermore, due to its health-promoting properties, such as anti-inflammatory, antioxidant, and antimicrobial effects, it has found applications in medicine and [...] Read more.
Curcumin is a natural bioactive compound of plant origin, characterised by a wide variety of properties that make it useful in numerous industries. Furthermore, due to its health-promoting properties, such as anti-inflammatory, antioxidant, and antimicrobial effects, it has found applications in medicine and animal husbandry. Unfortunately, curcumin has low bioavailability; its hydrophobic nature means it is poorly absorbed through the gastrointestinal tract, and it is rapidly metabolised in the liver. In recent years, research has been conducted into adding nanoencapsulated active ingredients, such as curcumin, to animal feed. This research aims to improve the bioavailability and stability of these ingredients, extend their shelf life, and enhance their absorption. These effects are expected to improve overall animal health, increase production efficiency, and enhance the quality of animal products. However, a significant challenge remains: the irreversible aggregation and chemical instability of bioactive substances due to the hydrolysis of their polymeric encapsulants, which can lead to toxic effects. This study utilised peripheral whole blood from five Blanc de Termonde rabbits. In vitro cell exposure was conducted using three distinct concentrations of nanoencapsulated curcumin (C1–C3: 10, 5.0, and 2.5 µg/mL) and a control. Cytotoxicity was determined by assessing viability using trypan blue exclusion, the comet assay, and the micronucleus assay. The results indicated that all tested concentrations of nanocurcumin significantly decreased the viability of blood cells to approximately 1–9%. In contrast, the encapsulation matrices themselves were not toxic (results were statistically significant). In the comet assay, the nanocurcumin formulations were toxic at all concentrations, and the results were statistically significant. Following exposure, the micronucleus assay revealed cell damage and a high percentage of apoptotic cells (up to 30% for Cur1 at 10 ug/mL). A significant number of binucleated cells with two micronuclei (BNCs + 2MN) were also observed, again for Cur1. In view of the considerable variation in the results from the individual tests, it is advisable to repeat the research using different matrix forms and concentrations of curcumin. Full article
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14 pages, 948 KB  
Article
Assessment of Landing Parameters in Patients with Chronic Ankle Instability
by Małgorzata Kowalczyk, Aleksandra Truszczyńska-Baszak, Krzysztof Dudziński and Barbara Łysoń-Ukłańska
J. Clin. Med. 2025, 14(17), 6074; https://doi.org/10.3390/jcm14176074 - 28 Aug 2025
Viewed by 465
Abstract
Background: The aim of this study was a qualitative assessment and quantitative assessment, i.e., the assessment of time to stability (TTS) before and after fatigue test, of landing in patients with chronic ankle instability, referred to as “copers”, in comparison to a control [...] Read more.
Background: The aim of this study was a qualitative assessment and quantitative assessment, i.e., the assessment of time to stability (TTS) before and after fatigue test, of landing in patients with chronic ankle instability, referred to as “copers”, in comparison to a control group of healthy persons. The indirect aim of the study was to develop a new method to assess more time precise measurement of TTS. Methods: The study involved 60 physically young active individuals aged 18 to 35 years. They were divided into three groups: the study population of 29 copers was divided into: I—14 persons with chronic one side ankle instability, study population II—15 persons with chronic bilateral ankle instability, and the control group included 31 persons without ankle instability. The study involved quantitative assessment of time to stability (TTS) after single-leg landing onto the HUR stabilometric platform from a 30 cm high platform before and after fatigue tests based on a modified Short-Term Fatigue Protocol. To conduct qualitative assessment of landing and to verify time to stability with video imaging, a video analysis was conducted. We used three cameras and two markers: on the malleolus lateralis of the fibula and on the malleolus medialis of the tibia. Each landing was subjectively assessed by a physiotherapist on a four-degree scale. A further biomechanic analysis was conducted only for the trials with a correct landing. The trials were repeated after a fatigue test. Results: There were significant differences before and after the fatigue test in qualitative landing analysis (p < 0.001) only for one jump for the right leg. In groups with unilateral and bilateral ankle instability, there was a higher percentage of landings with a considerable shift or unstable landings. The conducted dynamic test (TTS assessment) did not reveal significant differences between groups or after the fatigue test. Conclusions: Copers develop effective mechanisms of compensation, allowing them to participate in physical activities without symptoms of joint instability. Determining biomechanical differences between athletes who return to their sport and patients who develop chronic instability is important in the context of introducing adequate physiotherapy. Full article
(This article belongs to the Section Clinical Rehabilitation)
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14 pages, 2149 KB  
Article
Three-Dimensional-Printed Thermoplastic Polyurethane (TPU) Graft and H-Button Stabilization System for Intra-Articular Cranial Cruciate Ligament Reconstruction: Cadaveric Study
by Menna Nahla, Yara Abouelela, Mohammed Amer, Marwa Ali, Abdelbary Prince, Ayman Tolba and Ayman Mostafa
Vet. Sci. 2025, 12(8), 725; https://doi.org/10.3390/vetsci12080725 - 31 Jul 2025
Viewed by 527
Abstract
Cranial cruciate ligament (CrCL) rupture is a common orthopedic disorder in dogs, leading to stifle joint instability and progressive osteoarthritis. This study aimed to develop and biomechanically evaluate a novel intra-articular reconstruction system designed to mimic the natural ligament and restore joint stability [...] Read more.
Cranial cruciate ligament (CrCL) rupture is a common orthopedic disorder in dogs, leading to stifle joint instability and progressive osteoarthritis. This study aimed to develop and biomechanically evaluate a novel intra-articular reconstruction system designed to mimic the natural ligament and restore joint stability following CrCL excision. The system consisted of a 3D-printed thermoplastic polyurethane (TPU) graft, cerclage wire, and H-button fixation. Fourteen pelvic limbs from mature mixed-breed cadaveric dogs were used. The inclination angle, dimensions, volume, tensile strength, and elongation of the native CrCL were measured. Seven CrCL-deficient stifles were reconstructed using the proposed system and tested biomechanically. The native CrCL showed a significantly higher tensile strength than the TPU graft; however, the TPU demonstrated a greater flexibility. The reconstruction system successfully stabilized the joint and provided repeatable fixation. Significant correlations were found between CrCL volume and both age and body weight. These findings support the mechanical suitability of the proposed system for ex vivo stifle stabilization and highlight the potential of 3D-printed TPU in ligament reconstruction. Further in vivo studies are recommended to assess long-term performance, including implant integration, tissue remodeling, and clinical outcomes. Full article
(This article belongs to the Section Veterinary Surgery)
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23 pages, 869 KB  
Article
Cognitive Behavioral Therapy for Muscle Dysmorphia and Anabolic Steroid-Related Psychopathology: A Randomized Controlled Trial
by Metin Çınaroğlu, Eda Yılmazer, Selami Varol Ülker and Gökben Hızlı Sayar
Pharmaceuticals 2025, 18(8), 1081; https://doi.org/10.3390/ph18081081 - 22 Jul 2025
Viewed by 1166
Abstract
Background/Objectives: Muscle dysmorphia (MD), a subtype of body dysmorphic disorder, is prevalent among males who engage in the non-medical use of anabolic–androgenic steroids (AASs) and performance-enhancing drugs (PEDs). These individuals often experience severe psychopathology, including mood instability, compulsivity, and a distorted body [...] Read more.
Background/Objectives: Muscle dysmorphia (MD), a subtype of body dysmorphic disorder, is prevalent among males who engage in the non-medical use of anabolic–androgenic steroids (AASs) and performance-enhancing drugs (PEDs). These individuals often experience severe psychopathology, including mood instability, compulsivity, and a distorted body image. Despite its clinical severity, no randomized controlled trials (RCTs) have evaluated structured psychological treatments in this subgroup. This study aimed to assess the efficacy of a manualized cognitive behavioral therapy (CBT) protocol in reducing MD symptoms and associated psychological distress among male steroid users. Results: Participants in the CBT group showed significant reductions in MD symptoms from the baseline to post-treatment (MDDI: p < 0.001, d = 1.12), with gains sustained at follow-up. Large effect sizes were also observed in secondary outcomes including depressive symptoms (PHQ-9: d = 0.98), psychological distress (K10: d = 0.93), disordered eating (EDE-Q: d = 0.74), and exercise addiction (EAI: d = 1.07). No significant changes were observed in the control group. Significant group × time interactions were found for all outcomes (all p < 0.01), indicating CBT’s specific efficacy. Discussion: This study provides the first RCT evidence that CBT significantly reduces both core MD symptoms and steroid-related psychopathology in men engaged in AAS/PED misuse. Improvements extended to mood, body image perception, and compulsive exercise behaviors. These findings support CBT’s transdiagnostic applicability in addressing both the cognitive–behavioral and affective dimensions of MD. Materials and Methods: In this parallel-group, open-label RCT, 59 male gym-goers with DSM-5-TR diagnoses of MD and a history of AAS/PED use were randomized to either a 12-week CBT intervention (n = 30) or a waitlist control group (n = 29). CBT sessions were delivered weekly online and targeted distorted muscularity beliefs, compulsive behaviors, and emotional dysregulation. Primary and secondary outcomes—Muscle Dysmorphic Disorder Inventory (MDDI), PHQ-9, K10, EDE-Q, EAI, and BIG—were assessed at the baseline, post-treatment, and 3-month follow-up. A repeated-measures ANOVA and paired t-tests were used to analyze time × group interactions. Conclusions: CBT offers an effective, scalable intervention for individuals with muscle dysmorphia complicated by anabolic steroid use. It promotes broad psychological improvement and may serve as a first-line treatment option in high-risk male fitness populations. Future studies should examine long-term outcomes and investigate implementation in diverse clinical and cultural contexts. Full article
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25 pages, 4994 KB  
Article
Dynamic Slope Stability Assessment Under Blast-Induced Ground Vibrations in Open-Pit Mines: A Pseudo-Static Limit Equilibrium Approach
by Sami Ullah, Gaofeng Ren, Yongxiang Ge, Muhammad Burhan Memon, Eric Munene Kinyua and Theoneste Ndayiragije
Sustainability 2025, 17(14), 6642; https://doi.org/10.3390/su17146642 - 21 Jul 2025
Viewed by 1015
Abstract
Blasting is one of the most widely used and cost-effective techniques for rock excavation and fragmentation in open-pit mining, particularly for large-scale operations. However, repeated or poorly controlled blasting can generate excessive ground vibrations that threaten slope stability by causing structural damage, fracturing [...] Read more.
Blasting is one of the most widely used and cost-effective techniques for rock excavation and fragmentation in open-pit mining, particularly for large-scale operations. However, repeated or poorly controlled blasting can generate excessive ground vibrations that threaten slope stability by causing structural damage, fracturing of the rock mass, and potential failure. Evaluating the effects of blast-induced vibrations is essential to ensure safe and sustainable mining operations. This study investigates the impact of blasting-induced vibrations on slope stability at the Saindak Copper-Gold Open-Pit Mine in Pakistan. A comprehensive dataset was compiled, including field-monitored ground vibration measurements—specifically peak particle velocity (PPV) and key blast design parameters such as spacing (S), burden (B), stemming length (SL), maximum charge per delay (MCPD), and distance from the blast point (D). Geomechanical properties of slope-forming rock units were validated through laboratory testing. Slope stability was analyzed using pseudo-static limit equilibrium methods (LEMs) based on the Mohr–Coulomb failure criterion, employing four approaches: Fellenius, Janbu, Bishop, and Spencer. Pearson and Spearman correlation analyses quantified the influence of blasting parameters on slope behavior, and sensitivity analysis determined the cumulative distribution of slope failure and dynamic response under increasing seismic loads. FoS values were calculated for both east and west pit slopes under static and dynamic conditions. Among all methods, Spencer consistently yielded the highest FoS values. Under static conditions, FoS was 1.502 for the east slope and 1.254 for the west. Under dynamic loading, FoS declined to 1.308 and 1.102, reductions of 12.9% and 11.3%, respectively, as calculated using the Spencer method. The east slope exhibited greater stability due to its gentler angle. Correlation analysis revealed that burden had a significant negative impact (r = −0.81) on stability. Sensitivity analysis showed that stability deteriorates notably when PPV exceeds 10.9 mm/s. Although daily blasting did not critically compromise stability, the west slope showed greater vulnerability, underscoring the need for stricter control of blasting energy to mitigate vibration-induced instability and promote long-term operational sustainability. Full article
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12 pages, 1682 KB  
Article
Microsatellite Instability and BAT-26 Marker Expression in a Mexican Prostate Cancer Population with Different Gleason Scores
by Ana K. Flores-Islas, Manuel A. Rico-Méndez, Marisol Godínez-Rubí, Martha Arisbeth Villanueva-Pérez, Erick Sierra-Díaz, Ana Laura Pereira-Suárez, Saul A. Beltrán-Ontiveros, Perla Y. Gutiérrez-Arzapalo, José M. Moreno-Ortiz and Adrián Ramírez-de-Arellano
Diseases 2025, 13(7), 202; https://doi.org/10.3390/diseases13070202 - 30 Jun 2025
Viewed by 557
Abstract
Background/Objectives: Prostate cancer (PCa) is one of the most common cancers in men worldwide. While standard treatments often provide good initial results, many patients eventually develop resistance and experience a more aggressive relapse. Microsatellite instability (MSI) involves variations in the lengths of microsatellite [...] Read more.
Background/Objectives: Prostate cancer (PCa) is one of the most common cancers in men worldwide. While standard treatments often provide good initial results, many patients eventually develop resistance and experience a more aggressive relapse. Microsatellite instability (MSI) involves variations in the lengths of microsatellite base repeats in cells. Assessing the frequency of MSI is essential, as it may identify candidates for immune checkpoint inhibitors, which have shown promising outcomes. This study focuses on evaluating the MSI frequency in Mexican PCa patients and exploring its potential relationship with tumor aggressiveness. Methods: In this study, 116 formalin-fixed paraffin-embedded tumoral tissue biopsies from Mexican patients with PCa were collected from Hospital Civil de Culiacán and Pathology and Nephropathology, Diagnosis and Research Center, in the period from 2021 to 2024. The Gleason score was assessed, and the MSI was performed by multiplex PCR with a panel of five markers (NR-27, NR-21, NR-24, BAT-25, and BAT-26). High microsatellite instability (MSI-H) was defined as two or more unstable markers, low microsatellite instability (MSI-L) as an unstable marker, and microsatellite stability (MSS) as no unstable marker. Results: We found 19.83% (23/116) MSI PCa patients, of which 21.74% (5/23) were MSI-H, and 78.26% (18/23) were MSI-L. We found a major distribution of MSI-positive cases (50% (11/22)) in Gleason score 9 patients, corresponding to prognostic group 5. In addition, we found most of the instability in the BAT-26 marker in MSI PCa patients (60.87% (14/23)). Conclusions: This study is the first to evaluate the frequency of MSI in PCa within the Mexican population. Among the Mexican patients with MSI-positive PCa, there was a predominant Gleason score 9 and a majority instability of the BAT-26 marker. Full article
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22 pages, 3499 KB  
Article
Dynamic Behavior of the Fractional-Order Ananthakrishna Model for Repeated Yielding
by Hongyi Zhu and Liping Yu
Fractal Fract. 2025, 9(7), 425; https://doi.org/10.3390/fractalfract9070425 - 28 Jun 2025
Viewed by 400
Abstract
This paper introduces and analyzes a novel fractional-order Ananthakrishna model. The stability of its equilibrium points is first investigated using fractional-order stability criteria, particularly in regions where the corresponding integer-order model exhibits instability. A linear finite difference scheme is then developed, incorporating an [...] Read more.
This paper introduces and analyzes a novel fractional-order Ananthakrishna model. The stability of its equilibrium points is first investigated using fractional-order stability criteria, particularly in regions where the corresponding integer-order model exhibits instability. A linear finite difference scheme is then developed, incorporating an accelerated L1 method for the fractional derivative. This enables a detailed exploration of the model’s dynamic behavior in both the time domain and phase plane. Numerical simulations, including Lyapunov exponents, bifurcation diagrams, phase and time diagrams, demonstrate that the fractional model exhibits stable and periodic behaviors across various fractional orders. Notably, as the fractional order approaches a critical threshold, the time required to reach stability increases significantly, highlighting complex stability-transition dynamics. The computational efficiency of the proposed scheme is also validated, showing linear CPU time scaling with respect to the number of time steps, compared to the nearly quadratic growth of the classical L1 and Grünwald-Letnikow schemes, making it more suitable for long-term simulations of complex fractional-order models. Finally, four types of stress-time curves are simulated based on the fractional Ananthakrishna model, corresponding to both stable and unstable domains, effectively capturing and interpreting experimentally observed repeated yielding phenomena. Full article
(This article belongs to the Special Issue Modeling and Dynamic Analysis of Fractional-Order Systems)
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18 pages, 6079 KB  
Article
Integrative Genomic and Cytogenetic Analyses Reveal the Landscape of Typical Tandem Repeats in Water Hyacinth
by Liqing Feng, Ying Zhuang, Dagang Tian, Linwei Zhou, Jinbin Wang and Jingping Fang
Horticulturae 2025, 11(6), 657; https://doi.org/10.3390/horticulturae11060657 - 10 Jun 2025
Viewed by 562
Abstract
Tandem repeats in eukaryotic genomes exhibit intrinsic instability that drives rapid evolutionary diversification. However, their evolutionary dynamics in allopolyploid species such as the water hyacinth (Pontederia crassipes or Eichhornia crassipes) remain largely unexplored. Our study used integrated genomic and cytogenetic analyses [...] Read more.
Tandem repeats in eukaryotic genomes exhibit intrinsic instability that drives rapid evolutionary diversification. However, their evolutionary dynamics in allopolyploid species such as the water hyacinth (Pontederia crassipes or Eichhornia crassipes) remain largely unexplored. Our study used integrated genomic and cytogenetic analyses of this allotetraploid species to characterize five representative tandem repeats, revealing distinct genomic distribution patterns and copy number polymorphisms. The highly abundant centromeric tandem repeat, putative CentEc, was co-localized with the centromeric retrotransposon CREc, indicating conserved centromeric architecture. Remarkably, putative CentEc sequences showed high sequence conservation (91–100%) despite subgenome divergence, indicative of active concerted evolution. Fluorescence in situ hybridization (FISH) analysis showed ubiquitous telomeric repeats across all chromosomes, while an interstitial chromosome region tandem repeat (ICREc) displayed chromosome-specific localization, both exhibiting copy number variation. Furthermore, differential rDNA organization was observed. 5S rDNA was detected on a single chromosome pair, whereas 35S rDNA exhibited multichromosomal distribution with varying intensities. A comparative analysis of subgenome-specific rDNA sequences revealed substantial heterogeneity in both 5S and 35S rDNA units, suggesting subgenome-biased evolutionary trajectories. Collectively, these findings elucidate the structural and evolutionary significance of tandem repeats in shaping the water hyacinth genome, highlighting mechanisms of concerted evolution and subgenome-biased adaptation in invasive polyploids. Full article
(This article belongs to the Special Issue Latest Advances and Prospects in Germplasm of Tropical Fruits)
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9 pages, 1703 KB  
Case Report
Long-Read Sequencing Identifies Mosaic Sequence Variations in Friedreich’s Ataxia-GAA Repeats
by Joohyun Park, Claudia Dufke, Zofia Fleszar, Michael Schlotterbek, Elena Buena-Atienza, Lara G. Stühn, Caspar Gross, Marc Sturm, Stephan Ossowski, Ludger Schöls, Olaf Riess and Tobias B. Haack
Int. J. Mol. Sci. 2025, 26(11), 4969; https://doi.org/10.3390/ijms26114969 - 22 May 2025
Viewed by 936
Abstract
Friedreich’s ataxia (FRDA) is an autosomal recessive neurodegenerative disorder characterized by ataxia, sensory loss and pyramidal signs. While the majority of FRDA cases are caused by biallelic GAA trinucleotide repeat expansions in intron 1 of FXN, there is a subset of patients harboring [...] Read more.
Friedreich’s ataxia (FRDA) is an autosomal recessive neurodegenerative disorder characterized by ataxia, sensory loss and pyramidal signs. While the majority of FRDA cases are caused by biallelic GAA trinucleotide repeat expansions in intron 1 of FXN, there is a subset of patients harboring a heterozygous pathogenic small variant compound-heterozygous with a GAA repeat expansion. We report on the diagnostic journey of a 21-year-old patient who was clinically suspected of having FRDA at the age of 12 years. Genetic testing included fragment analysis, gene panel analysis and exome sequencing, which only detected one pathogenic heterozygous missense variant (c.389 G>T,p.Gly130Val) in FXN. Although conventional repeat analyses failed to detect GAA expansions in our patient, subsequent short-read genome sequencing (GS) indicated a potential GAA repeat expansion. This finding was confirmed by long-read GS, which in addition revealed a complex pattern of interruptions. Both large and small GAA expansions with divergent interruptions containing G, A, GA, GAG and/or GAAG sequences were present within one allele, indicating mosaic sequence variations. Our findings underscore the complexity of repeat expansions which can exhibit both interruptions and somatic instability. We also highlight the utility of long-read GS in unraveling intricate genetic profiles, ultimately contributing to more accurate diagnoses in clinical practice. Full article
(This article belongs to the Special Issue Genetic Testing in Molecular Pathology and Diagnosis)
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Article
Utilization of Native CRISPR-Cas9 System for Expression of Glucagon-like Peptide-1 in Lacticaseibacillus paracasei
by Mumin Zheng, Shuwen Zhang, Yunna Wang, Ning Xie, Xiaodan Wang, Jiaping Lv, Xiaoyang Pang and Xu Li
Foods 2025, 14(10), 1785; https://doi.org/10.3390/foods14101785 - 17 May 2025
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Abstract
Type 2 diabetes is one of the main causes of cardiovascular diseases, kidney diseases, and visual impairments, posing a global healthcare challenge. The current treatment of this disease, involving glucagon-like peptide-1 (GLP-1), is faced with problems such as frequent injections and plasmid instability. [...] Read more.
Type 2 diabetes is one of the main causes of cardiovascular diseases, kidney diseases, and visual impairments, posing a global healthcare challenge. The current treatment of this disease, involving glucagon-like peptide-1 (GLP-1), is faced with problems such as frequent injections and plasmid instability. In this study, we used the native clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 (CRISPR-Cas9) system of Lacticaseibacillus paracasei to develop a novel, genetically stable, and orally administrable strain expressing human GLP-1. Integration and subsequent expression of glp-1 gene were confirmed by genomic sequencing, qPCR, and Nano LC-MS. The engineered strain demonstrated stable genomic integration and sustained high-level expression of GLP-1 over multiple generations. This innovative approach provides a promising strategy for the oral delivery of therapeutic peptides, potentially enhancing patient compliance and improving the treatment of diabetes and other chronic diseases requiring peptide-based therapies. Full article
(This article belongs to the Section Food Microbiology)
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