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Calcific aortic stenosis (CAS) is a newly emerging pandemic in elderly individuals due to the aging of the population in the world. Surgical Aortic Valve Replacement (SAVR) and Transcatheter Aortic Valve Replacement (TAVR) are the cornerstone of the management of severe aortic stenosis accompanied by one or more symptoms. Moreover, an appropriate interventional treatment of CAS, in elderly patients, is a very complex decision for heart teams, to avoid bad outcomes such as operative mortality, cardiovascular and all-cause death, hospitalization for heart failure, worsening of quality of life. In fact, CAS in the elderly is not only a focal valve disease, but a very complex clinical picture with different risk factors and etiologies, differing underlying pathophysiology, large phenotypic heterogeneity in a context of subjective biological, phenotypic and functional aging until frailty and disability. In this review, we analyzed separately and in a more integrated manner, the natural and prognostic histories of the progression of aortic stenosis, the phenotypes of myocardial damage and heart failure, within the metrics and aging trajectory. The aim is to suggest, during the clinical timing of valve disease, the best interval time for an appropriate and effective interventional treatment in each older patient, beyond subjective symptoms by integration of clinical, geriatric, chemical, and advanced imaging biomarkers. Full article

(This article belongs to the Section Cardiology)

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20 pages, 2267 KiB

Open AccessArticle

Alterations in the Platelet Transcriptome Mediate Prenatal Thirdhand Smoke Exposure Associated Thrombogenicity via Integrated miRNA-mRNA Regulatory Networks

by Hamdy E. A. Ali, Ahmed B. Alarabi, Fatima Z. Alshbool and Fadi T. Khasawneh

Int. J. Mol. Sci. 2025, 26(15), 7633; https://doi.org/10.3390/ijms26157633 - 7 Aug 2025

Abstract

Cigarette smoking is acknowledged as the most preventable risk factor for thrombogenesis-associated cardiovascular disease. Mice prenatally exposed to the thirdhand smoke (THS) form of tobacco exhibited a higher tendency to develop occlusive thrombosis, along with enhancement of several platelet functional responses. Our objective was to investigate whether prenatal (in utero) THS exposure impacts the platelet transcriptome, resulting in enhanced platelet functional responses, thereby underlying THS-associated thrombogenicity. Blood samples obtained from twenty male mice prenatally exposed to THS, along with an equal number of age-matched male mice exposed to clean air (CA) as a control, were divided into pools of five animals and used to prepare leukocyte and red blood cell-depleted platelets. RNA sequencing for mRNA and microRNA (miRNA) was utilized to analyze and compare the platelet expression profiles of the two exposure groups. RNA seq analyses revealed distinct changes in both gene expression and miRNA profiles, with 448 coding genes and 18 miRNAs significantly altered between the two groups. miRNA–mRNA interaction analysis highlighted 14 differentially expressed miRNAs that potentially target 120 of the differentially expressed genes in our data set. Interestingly, altered genes in miRNA–mRNA pairs were functionally enriched into pathways associated with platelet physiology, including platelet activation, signaling and aggregation, and cellular response to chemical stimuli. Our findings establish—for the first time—that prenatal exposure to THS modifies the platelet transcriptome, thereby rendering platelets hypersensitive to stimuli and more prone to thrombogenicity. Additionally, we illuminate the coordinated function of platelet miRNA and mRNA targets in mediating this response. Full article

(This article belongs to the Special Issue MicroRNAs and mRNA in Human Health and Disease)

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22 pages, 1215 KiB

Open AccessArticle

Gas Atmosphere Innovation Applied to Prolong the Shelf Life of ‘Regina’ Sweet Cherries

by Rodrigo Neira-Ojeda, Sebastián Rodriguez, Cristian Hernández-Adasme, Violeta Muñoz, Dakary Delgadillo, Bo Sun, Xiao Yang and Victor Hugo Escalona

Plants 2025, 14(15), 2440; https://doi.org/10.3390/plants14152440 - 6 Aug 2025

Abstract

In this study, the impact of moderate and high CO₂ and O₂ levels was compared to low and moderate gas combinations during prolonged storage on the quality of Regina sweet cherries harvested in different maturity stages, particularly in terms of decreasing internal browning. Fruits were harvested in two different maturity stages (Light and Dark Mahogany skin color) and stored in CA of 15% CO₂ + 10% O₂; 10% CO₂ + 10% O₂; 10% CO₂ + 5% O₂; 5% CO₂ + 5% O₂ and MA of 4 to 5% CO₂ + 16 to 17% O₂ for 30 and 40 days at 0 °C and 90% RH, followed by a marketing period. After the storage, both maturity stages significantly reduced internal browning, decay, and visual quality losses in CA with 10–15% CO₂ and 10% O₂. In addition, it preserved luminosity, total soluble solids (TSSs), titratable acidity (TA), and bioactive compounds such as anthocyanins and phenols. This treatment also maintained the visual appearance of the sweet cherries, favoring their market acceptance. At the same time, the light red fruits showed a better general quality compared to darker color after the storage. In conclusion, a controlled atmosphere with optimized CO₂ and O₂ concentrations, together with harvesting with a Light Mahogany external color, represents an effective strategy to extend the shelf life of Regina sweet cherries up to 40 days plus the marketing period, maintaining their physical and sensory quality for export markets. Full article

(This article belongs to the Special Issue Postharvest Quality and Physiology of Vegetables and Fruits)

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20 pages, 2614 KiB

Open AccessArticle

Porphyrin-Modified Polyethersulfone Ultrafiltration Membranes for Enhanced Bacterial Inactivation and Filtration Performance

by Funeka Matebese, Nonkululeko Malomane, Meladi L. Motloutsi, Richard M. Moutloali and Muthumuni Managa

Membranes 2025, 15(8), 239; https://doi.org/10.3390/membranes15080239 - 6 Aug 2025

Abstract

Municipal wastewaters pose a severe risk to the environment and human health when discharged untreated. This is due to their high content of pathogens, such as viruses and bacteria, which can cause diseases like cholera. Herein, the research and development of porphyrin-modified polyethersulfone (PES) ultrafiltration (UF) membranes was conducted to improve bacterial inactivation in complex municipal wastewater and enhance the fouling resistance and filtration performance. The synthesis and fabrication of porphyrin nanofillers and the resultant membrane characteristics were studied. The incorporation of porphyrin-based nanofillers improved the membrane’s hydrophilicity, morphology, and flux (247 Lm⁻² h⁻¹), with the membrane contact angle (CA) decreasing from 90° to ranging between 58° and 50°. The membrane performance was monitored for its flux, antifouling properties, reusability potential, municipal wastewater, and humic acid. The modified membranes demonstrated an effective application in wastewater treatment, achieving notable antibacterial activity, particularly under light exposure. The In-BP@SW/PES membrane demonstrated effective antimicrobial photodynamic effects against both Gram-positive S. aureus and Gram-negative E. coli. It achieved at least a 3-log reduction in bacterial viability, meeting Food and Drug Administration (FDA) standards for efficient antimicrobial materials. Among the variants tested, membranes modified with In-PB@SW nanofillers exhibited superior antifouling properties with flux recovery ratios (FRRs) of 78.9% for the humic acid (HA) solution and 85% for the municipal wastewater (MWW), suggesting a strong potential for long-term filtration use. These results highlight the promise of porphyrin-functionalized membranes as multifunctional tools in advanced water treatment technologies. Full article

(This article belongs to the Special Issue Membrane and Other Innovative Technologies for Water Purification: Design, Development, and Application)

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21 pages, 9310 KiB

Open AccessArticle

Synergistic Regulation of Pigment Cell Precursors’ Differentiation and Migration by ednrb1a and ednrb2 in Nile Tilapia

by Zilong Wen, Jinzhi Wu, Jiawen Yao, Fugui Fang, Siyu Ju, Chenxu Wang, Xingyong Liu and Deshou Wang

Cells 2025, 14(15), 1213; https://doi.org/10.3390/cells14151213 - 6 Aug 2025

Abstract

The evolutionary loss of ednrb2 in specific vertebrate lineages, such as mammals and cypriniform fish, raises fundamental questions about its functional necessity and potential redundancy or synergy with paralogous endothelin receptors in pigment cell development. In teleosts possessing both ednrb1a and ednrb2 (e.g., Nile tilapia), their respective and combined roles in regulating neural crest-derived pigment cell precursors remains unresolved. Using CRISPR/Cas9, we generated single and double ednrb mutants to dissect their functions. We demonstrated that ednrb1a and ednrb2 synergistically govern the differentiation and migration of iridophore precursors. While ednrb1a is broadly essential for iridophore development, ednrb2 plays a unique and indispensable role in the colonization of iridophores in the dorsal iris. Double mutants exhibit near-complete iridophore loss; severe depletion of melanophores, xanthophores, and erythrophores; and a striking, fertile, transparent phenotype. Crucially, this iridophore deficiency does not impair systemic guanine synthesis pathways. mRNA rescue experiments confirmed mitfa as a key downstream effector within the Ednrb signaling cascade. This work resolves the synergistic regulation of pigment cell fates by Ednrb receptors and establishes a mechanism for generating transparent ermplasm. Full article

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21 pages, 1788 KiB

Open AccessArticle

Investigation, Prospects, and Economic Scenarios for the Use of Biochar in Small-Scale Agriculture in Tropical

by Vinicius John, Ana Rita de Oliveira Braga, Criscian Kellen Amaro de Oliveira Danielli, Heiriane Martins Sousa, Filipe Eduardo Danielli, Newton Paulo de Souza Falcão, João Guerra, Dimas José Lasmar and Cláudia S. C. Marques-dos-Santos

Agriculture 2025, 15(15), 1700; https://doi.org/10.3390/agriculture15151700 - 6 Aug 2025

Abstract

This study investigates the production and economic feasibility of biochar for smallholder and family farms in Central Amazonia, with potential implications for other tropical regions. The costs of construction of a prototype mobile kiln and biochar production were evaluated, using small-sized biomass from acai (Euterpe oleracea Mart.) agro-industrial residues as feedstock. The biochar produced was characterised in terms of its liming capacity (calcium carbonate equivalence, CaCO_3eq), nutrient content via organic fertilisation methods, and ash analysis by ICP-OES. Field trials with cowpea assessed economic outcomes, as well scenarios of fractional biochar application and cost comparison between biochar production in the prototype kiln and a traditional earth-brick kiln. The prototype kiln showed production costs of USD 0.87–2.06 kg⁻¹, whereas traditional kiln significantly reduced costs (USD 0.03–0.08 kg⁻¹). Biochar application alone increased cowpea revenue by 34%, while combining biochar and lime raised cowpea revenues by up to 84.6%. Owing to high input costs and the low value of the crop, the control treatment generated greater net revenue compared to treatments using lime alone. Moreover, biochar produced in traditional kilns provided a 94% increase in net revenue compared to liming. The estimated externalities indicated that carbon credits represented the most significant potential source of income (USD 2217 ha⁻¹). Finally, fractional biochar application in ten years can retain over 97% of soil carbon content, demonstrating potential for sustainable agriculture and carbon sequestration and a potential further motivation for farmers if integrated into carbon markets. Public policies and technological adaptations are essential for facilitating biochar adoption by small-scale tropical farmers. Full article

(This article belongs to the Special Issue Converting and Recycling of Agroforestry Residues)

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15 pages, 1805 KiB

Open AccessArticle

Indoor Application of Coupled FLOCponics System with Caipira Lettuce (Lactuca sativa) Affects the Growth Performance and Water Characteristics of Far Eastern Catfish (Silurus asotus) and Tropical Eel (Anguilla bicolor)

by Jun Seong Park, Hae Seung Jeong, Jeong-ho Lee and Ju-ae Hwang

Animals 2025, 15(15), 2305; https://doi.org/10.3390/ani15152305 - 6 Aug 2025

Abstract

In this study, we sought to improve the productivity of Far Eastern catfish (Silurus asotus) and tropical eel (Anguilla bicolor), which are high-value fish species in the Republic of Korea, as well as that of associated crops by applying biofloc technology (BFT)-based aquaponics systems. The following three systems were used: the flow-through system (FTS), BFT, and BFT aquaponics system (BAPs). Caipira lettuce (Lactuca sativa) was utilized and hydroponics (HP) was implemented to compare crop productivity. After 42 days of treatment, the BAPs and BFT systems improved fish productivity, with weight gain rates of 134.47 ± 1.80% in BAPs-cat, 130.38 ± 0.95% in BFT, and 114.21 ± 6.62% in FTS for S. asotus, and 70.61 ± 3.26% in BAPs-eel, 62.37 ± 7.04% in BFT, and 47.83 ± 1.09% in FTS for A. bicolor. During the experiment, the total ammonia nitrogen and NO₂⁻-N concentrations were stable in all plots. In the case of NO₃⁻-N, BFT showed an increasing tendency while both BAPs showed a decrease compared with that of the BFT. BAPs-cat (total weight: 224.1 ± 6.37 g) and HP (220.3 ± 7.17 g) resulted in similar growth. However, in BAPs-eel was 187.7 ± 3.46 g due to root degradation. Water content analysis showed that BAPs-cat and BAPs-eel contained sufficient K, Ca, P, and S, which are important for crop growth. Overall, the effect of BAPs on fish growth was higher than that of FTS. This study reveals that integrating BFT with aquaponics improves productivity for high-value fish and associated crops while maintaining stable water quality. This method offers sustainable, efficient production, reduces environmental impact, and provides insights for future research in sustainable aquaculture practices. Full article

(This article belongs to the Special Issue Innovations in Aquaculture: New Technologies, Culture Systems and Integration of Emerging Species)

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21 pages, 3451 KiB

Open AccessArticle

Transcriptional Repression of CCL2 by K_Ca3.1 K⁺ Channel Activation and LRRC8A Anion Channel Inhibition in THP-1-Differentiated M₂ Macrophages

by Miki Matsui, Junko Kajikuri, Hiroaki Kito, Yohei Yamaguchi and Susumu Ohya

Int. J. Mol. Sci. 2025, 26(15), 7624; https://doi.org/10.3390/ijms26157624 - 6 Aug 2025

Abstract

We investigated the role of the intermediate-conductance, Ca²⁺-activated K⁺ channel K_Ca3.1 and volume-regulatory anion channel LRRC8A in regulating C-C motif chemokine ligand 2 (CCL2) expression in THP-1-differentiated M₂ macrophages (M₂-MACs), which serve as a useful model for studying tumor-associated macrophages (TAMs). CCL2 is a potent chemoattractant involved in the recruitment of immunosuppressive cells and its expression is regulated through intracellular signaling pathways such as ERK, JNK, and Nrf2 in various types of cells including macrophages. The transcriptional expression of CCL2 was suppressed in M₂-MACs following treatment with a K_Ca3.1 activator or an LRRC8A inhibitor via distinct signaling pathways: ERK–CREB2 and JNK–c-Jun pathways for K_Ca3.1, and the NOX2–Nrf2–CEBPB pathway for LRRC8A. Under in vitro conditions mimicking the elevated extracellular K⁺ concentration ([K⁺]_e) characteristic of the tumor microenvironment (TME), CCL2 expression was markedly upregulated, and this increase was reversed by treatment with them in M₂-MACs. Additionally, the WNK1–AMPK pathway was, at least in part, involved in the high [K⁺]_e-induced upregulation of CCL2. Collectively, modulating K_Ca3.1 and LRRC8A activities offers a promising strategy to suppress CCL2 secretion in TAMs, potentially limiting the CCL2-induced infiltration of immunosuppressive cells (TAMs, T_regs, and MDSCs) in the TME. Full article

(This article belongs to the Special Issue Regulation of Ion Channels and Transporters)

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19 pages, 1680 KiB

Open AccessArticle

Role of Endogenous Galectin-3 on Cell Biology of Immortalized Retinal Pigment Epithelial Cells In Vitro †

by Caspar Liesenhoff, Marlene Hillenmayer, Caroline Havertz, Arie Geerlof, Daniela Hartmann, Siegfried G. Priglinger, Claudia S. Priglinger and Andreas Ohlmann

Int. J. Mol. Sci. 2025, 26(15), 7622; https://doi.org/10.3390/ijms26157622 - 6 Aug 2025

Abstract

Galectin-3 is a multifunctional protein that is associated with diseases of the chorioretinal interface, in which the retinal pigment epithelium (RPE) plays a central role in disease development and progression. Since galectin-3 can function extracellularly as well as intracellularly via different mechanisms, we developed an immortalized human RPE cell line (ARPE-19) with a knockdown for galectin-3 expression (ARPE-19/LGALS3^+/−) using a sgRNA/Cas9 all-in-one expression vector. By Western blot analysis, a reduced galectin-3 expression of approximately 48 to 60% in heterozygous ARPE-19/LGALS3^+/− cells was observed when compared to native controls. Furthermore, ARPE-19/LGALS3^+/− cells displayed a flattened, elongated phenotype with decreased E-cadherin as well as enhanced N-cadherin and α-smooth muscle actin mRNA expression, indicating an epithelial–mesenchymal transition of the cells. Compared to wildtype controls, ARPE-19/LGALS3^+/− cells had significantly reduced metabolic activity to 86% and a substantially decreased proliferation to 73%. Furthermore, an enhanced cell adhesion and a diminished migration of immortalized galectin-3 knockdown RPE cells was observed compared to native ARPE-19 cells. Finally, by Western blot analysis, reduced pAKT, pERK1/2, and β-catenin signaling were detected in ARPE-19/LGALS3^+/− cells when compared to wildtype controls. In summary, in RPE cells, endogenous galectin-3 appears to be essential for maintaining the epithelial phenotype as well as cell biological functions such as metabolism, proliferation, or migration, effects that might be mediated via a decreased activity of the AKT, ERK1/2, and β-catenin signaling pathways. Full article

(This article belongs to the Special Issue Galectins (Gals), 2nd Edition)

30 pages, 4444 KiB

Open AccessArticle

Unveiling the Potential of Novel Ternary Chalcogenide SrHfSe₃ for Eco-Friendly, Self-Powered, Near-Infrared Photodetectors: A SCAPS-1D Simulation Study

by Salah Abdo, Ambali Alade Odebowale, Amer Abdulghani, Khalil As’ham, Sanjida Akter, Haroldo Hattori, Nicholas Kanizaj and Andrey E. Miroshnichenko

Sci 2025, 7(3), 113; https://doi.org/10.3390/sci7030113 - 6 Aug 2025

Abstract

Ternary chalcogenide-based sulfide materials with distorted morphologies such as BaZrS₃, CaZrS₃, and SrZrS₃, have recently gained much attention in optoelectronics and photovoltaics due to their high structural and thermal stability and compatibility with low-cost, earth-abundant synthesis routes. However, their relatively large bandgaps often limit their suitability for near-infrared (NIR) photodetectors. Here, we conducted a comprehensive investigation of SrHfSe₃, a ternary chalcogenide with an orthorhombic crystal structure and distinctive needle-like morphology, as a promising candidate for NIR photodetection. SrHfSe₃ exhibits a direct bandgap of 1.02 eV, placing it well within the NIR range. Its robust structure, high temperature stability, phase stability and natural abundance make it a compelling material for next-generation, self-powered NIR photodetectors. An in-depth analysis of the SrHfSe₃-based photodetector was performed using SCAPS-1D simulations, focusing on key performance metrics such as J–V behavior, photoresponsivity, and specific detectivity. Device optimization was achieved by thoroughly altering each layer thickness, doping concentrations, and defect densities. Additionally, the influence of interface defects, absorber bandgap, and operating temperature was assessed to enhance the photoresponse. Under optimal conditions, the device achieved a short-circuit current density (Jsc) of 45.88 mA/cm², an open-circuit voltage (Voc) of 0.7152 V, a peak photoresponsivity of 0.85 AW⁻¹, and a detectivity of 2.26 × 10¹⁴ Jones at 1100 nm. A broad spectral response spanning 700–1200 nm confirms its efficacy in the NIR region. These results position SrHfSe₃ as a strong contender for future NIR photodetectors and provide a foundation for experimental validation in advanced optoelectronic applications. Full article

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16 pages, 2868 KiB

Open AccessArticle

The Biocorrosion of a Rare Earth Magnesium Alloy in Artificial Seawater Containing Chlorella vulgaris

by Xinran Yao, Qi Fu, Guang-Ling Song and Kai Wang

Materials 2025, 18(15), 3698; https://doi.org/10.3390/ma18153698 - 6 Aug 2025

Abstract

In the medical field, magnesium (Mg) alloys have been widely used due to their excellent antibacterial properties and biodegradability. However, in the marine environment, the antibacterial effect may be greatly attenuated, and consequently, microorganisms in the ocean are likely to adhere to the surface of Mg alloys, resulting in biocorrosion damage, which is really troublesome in the maritime industry and can even be disastrous to the navy. Currently, there is a lack of research on the biocorrosion of Mg alloys that may find important applications in marine engineering. In this paper, the biocorrosion mechanism of the Mg alloy Mg-3Nd-2Gd-Zn-Zr caused by Chlorella vulgaris (C. vulgaris), a typical marine microalga, was studied. The results showed that the biomineralization process in the artificial seawater containing a low concentration of C. vulgaris cells was accelerated compared with that in the abiotic artificial seawater, leading to the deposition of CaCO₃ on the surface to inhibit the localized corrosion of the Mg alloy, whereas a high concentration of C. vulgaris cells produced a high content of organic acids at some sites through photosynthesis to significantly accelerate the surface film rupture at some sites and severe localized corrosion there, but meanwhile, it resulted in the formation of a more protective biomineralized film in the other areas to greatly alleviate the corrosion. The contradictory biocorrosion behaviors on the Mg-3Nd-2Gd-Zn-Zr alloy induced by C. vulgaris were finally explained by a mechanism proposed in the paper. Full article

(This article belongs to the Section Corrosion)

12 pages, 1530 KiB

Open AccessArticle

Effect of Aggregate Type on Asphalt–Aggregate Adhesion and Its Quantitative Characterization

by Liuxiao Chen, Junlin Li, Hao Xiang, Jun Zhang, Enlin Feng and Lin Kong

Materials 2025, 18(15), 3696; https://doi.org/10.3390/ma18153696 - 6 Aug 2025

Abstract

To study the effect of aggregate type on the adhesion between asphalt and aggregate, limestone, basalt, diabase, and 70# asphalt with SBS asphalt were selected. The mineral phase composition of the aggregates was analyzed by X-ray diffraction. The surface energy theory was used to calculate the adhesion work and the work of flaking. The modified water boiling method combined with image processing technology was used to quantitatively characterize the flaking behavior of the asphalt. The results show that the aggregate type is closely related to the asphalt–aggregate adhesion. The mineral compositions of different types of aggregates vary significantly, with limestone, being a strongly alkaline aggregate predominantly comprising CaCO₃, exhibiting better adhesion with asphalt. The contact angle test and modified boiling method also yielded the same results, and the adhesion relationship with asphalt was limestone > basalt > diabase. Image processing technology effectively characterizes the spalling situation of asphalt and conducts quantitative analysis. Full article

(This article belongs to the Section Construction and Building Materials)

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27 pages, 1483 KiB

Open AccessSystematic Review

Effectiveness of Virtual Reality-Based Training Versus Conventional Exercise Programs on Fall-Related Functional Outcomes in Older Adults with Various Health Conditions: A Systematic Review

by Krzysztof Kasicki, Ewa Klimek Piskorz, Łukasz Rydzik, Tadeusz Ambroży, Piotr Ceranowicz, Maria Belcarz Ciuraj, Paweł Król and Wiesław Błach

J. Clin. Med. 2025, 14(15), 5550; https://doi.org/10.3390/jcm14155550 - 6 Aug 2025

Abstract

Background/Objectives: The aim of this systematic review was to compare the effectiveness of virtual reality (VR)-based training with conventional exercise programs in improving functional outcomes related to fall risk among older adults with various health conditions. Methods: The review was conducted in accordance with the PRISMA 2020 guidelines and registered in PROSPERO (registration number CRD42022345678). The databases Scopus, PubMed, Web of Science, and EBSCO were searched up to 31 March 2025. Randomized controlled trials (RCTs) were included if they involved participants aged ≥60 years, a VR intervention lasting ≥6 weeks, and a control group performing traditional exercises or receiving usual care. Methodological quality was assessed using the PEDro scale, and a narrative synthesis was performed across four outcome domains: balance, mobility, cognitive function, and fall risk. Results: Seven RCTs were included in the analysis (totaling 664 participants). VR training was found to be at least as effective as conventional exercise in improving balance (e.g., Berg Balance Scale) and mobility (e.g., Timed Up and Go), with some studies showing superior effects of VR. One RCT demonstrated that combining VR with balance exercises (MIX) yielded the greatest improvements in muscle strength and physical performance. Additionally, two studies reported cognitive benefits (e.g., MoCA) and a 42% reduction in fall incidence within six months following VR intervention. The methodological quality of the included studies was moderate to high (PEDro score 5–9/10). Conclusions: VR-based training represents a safe and engaging supplement to geriatric rehabilitation, effectively improving balance, mobility, and, in selected cases, cognitive function, while also reducing fall risk. Full article

(This article belongs to the Section Geriatric Medicine)

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13 pages, 2759 KiB

Open AccessArticle

A Novel Serum-Based Bioassay for Quantification of Cancer-Associated Transformation Activity: A Case–Control and Animal Study

by Aye Aye Khine, Hsuan-Shun Huang, Pao-Chu Chen, Chun-Shuo Hsu, Ying-Hsi Chen, Sung-Chao Chu and Tang-Yuan Chu

Diagnostics 2025, 15(15), 1975; https://doi.org/10.3390/diagnostics15151975 - 6 Aug 2025

Abstract

Background/Objectives: The detection of ovarian cancer remains challenging due to the lack of reliable serum biomarkers that reflect malignant transformation rather than mere tumor presence. We developed a novel biotest using an immortalized human fallopian tube epithelial cell line (TY), which exhibits anchorage-independent growth (AIG) in response to cancer-associated serum factors. Methods: Sera from ovarian and breast cancer patients, non-cancer controls, and ID8 ovarian cancer-bearing mice were tested for AIG-promoting activity in TY cells. Results: TY cells (passage 96) effectively distinguished cancer sera from controls (68.50 ± 2.12 vs. 17.50 ± 3.54 colonies, p < 0.01) and correlated with serum CA125 levels (r = 0.73, p = 0.03) in ovarian cancer patients. Receiver operating characteristic (ROC) analysis showed high diagnostic accuracy (AUC = 0.85, cutoff: 23.75 colonies). The AIG-promoting activity was mediated by HGF/c-MET and IGF/IGF-1R signaling, as inhibition of these pathways reduced phosphorylation and AIG. In an ID8 mouse ovarian cancer model, TY-AIG colonies strongly correlated with tumor burden (r = 0.95, p < 0.01). Conclusions: Our findings demonstrate that the TY cell-based AIG assay is a sensitive and specific biotest for detecting ovarian cancer and potentially other malignancies, leveraging the fundamental hallmark of malignant transformation. Full article

(This article belongs to the Special Issue New Insights into the Diagnosis of Gynecological Diseases)

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21 pages, 3840 KiB

Open AccessFeature PaperArticle

Identification of CaVβ1 Isoforms Required for Neuromuscular Junction Formation and Maintenance

by Amélie Vergnol, Aly Bourguiba, Stephanie Bauché, Massiré Traoré, Maxime Gelin, Christel Gentil, Sonia Pezet, Lucile Saillard, Pierre Meunier, Mégane Lemaitre, Julianne Perronnet, Frederic Tores, Candice Gautier, Zoheir Guesmia, Eric Allemand, Eric Batsché, France Pietri-Rouxel and Sestina Falcone

Cells 2025, 14(15), 1210; https://doi.org/10.3390/cells14151210 - 6 Aug 2025

Abstract

Voltage-gated Ca²⁺ channels (VGCCs) are regulated by four CaVβ subunits (CaVβ1–CaVβ4), each showing specific expression patterns in excitable cells. While primarily known for regulating VGCC function, CaVβ proteins also have channel-independent roles, including gene expression modulation. Among these, CaVβ1 is expressed in skeletal muscle as multiple isoforms. The adult isoform, CaVβ1D, localizes at the triad and modulates CaV1 activity during Excitation–Contraction Coupling (ECC). In this study, we investigated the lesser-known embryonic/perinatal CaVβ1 isoforms and their roles in neuromuscular junction (NMJ) formation, maturation, and maintenance. We found that CaVβ1 isoform expression is developmentally regulated through differential promoter activation. Specifically, CaVβ1A is expressed in embryonic muscle and reactivated in denervated adult muscle, alongside the known CaVβ1E isoform. Nerve injury in adult muscle triggers a shift in promoter usage, resulting in re-expression of embryonic/perinatal Cacnb1A and Cacnb1E transcripts. Functional analyses using aneural agrin-induced AChR clustering on primary myotubes demonstrated that these isoforms contribute to NMJ formation. Additionally, their expression during early post-natal development is essential for NMJ maturation and long-term maintenance. These findings reveal previously unrecognized roles of CaVβ1 isoforms beyond VGCC regulation, highlighting their significance in neuromuscular system development and homeostasis. Full article

(This article belongs to the Section Tissues and Organs)

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