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30 pages, 8054 KB  
Article
A New, Discrete Model of Lindley Families: Theory, Inference, and Real-World Reliability Analysis
by Refah Alotaibi and Ahmed Elshahhat
Mathematics 2026, 14(3), 397; https://doi.org/10.3390/math14030397 - 23 Jan 2026
Viewed by 83
Abstract
Recent developments in discrete probability models play a crucial role in reliability and survival analysis when lifetimes are recorded as counts. Motivated by this need, we introduce the discrete ZLindley (DZL) distribution, a novel discretization of the continuous ZL law. Constructed using a [...] Read more.
Recent developments in discrete probability models play a crucial role in reliability and survival analysis when lifetimes are recorded as counts. Motivated by this need, we introduce the discrete ZLindley (DZL) distribution, a novel discretization of the continuous ZL law. Constructed using a survival-function approach, the DZL retains the analytical tractability of its continuous parent while simultaneously exhibiting a monotonically decreasing probability mass function and a strictly increasing hazard rate—properties that are rarely achieved together in existing discrete models. We derive key statistical properties of the proposed distribution, including moments, quantiles, order statistics, and reliability indices such as stress–strength reliability and the mean residual life. These results demonstrate the DZL’s flexibility in modeling skewness, over-dispersion, and heavy-tailed behavior. For statistical inference, we develop maximum likelihood and symmetric Bayesian estimation procedures under censored sampling schemes, supported by asymptotic approximations, bootstrap methods, and Markov chain Monte Carlo techniques. Monte Carlo simulation studies confirm the robustness and efficiency of the Bayesian estimators, particularly under informative prior specifications. The practical applicability of the DZL is illustrated using two real datasets: failure times (in hours) of 18 electronic systems and remission durations (in weeks) of 20 leukemia patients. In both cases, the DZL provides substantially better fits than nine established discrete distributions. By combining structural simplicity, inferential flexibility, and strong empirical performance, the DZL distribution advances discrete reliability theory and offers a versatile tool for contemporary statistical modeling. Full article
(This article belongs to the Special Issue Statistical Models and Their Applications)
11 pages, 1010 KB  
Article
Comparative Evaluation of the Translucency Properties of CAD/CAM Anterior Crowns
by Hatice Banu Özel, Mine Helvacıoğlu Özkardeş and Erkut Kahramanoğlu
Appl. Sci. 2026, 16(2), 663; https://doi.org/10.3390/app16020663 - 8 Jan 2026
Viewed by 178
Abstract
This study aimed to compare the translucency values of anterior crowns fabricated with ultra-high-translucent (UHT) zirconia, low-translucent (LT) lithium disilicate (LDS), and LT zirconia-reinforced lithium silicate (ZLS) glass-ceramics. In total, 48 central incisor crowns (n = 12) were fabricated from IPS e.max [...] Read more.
This study aimed to compare the translucency values of anterior crowns fabricated with ultra-high-translucent (UHT) zirconia, low-translucent (LT) lithium disilicate (LDS), and LT zirconia-reinforced lithium silicate (ZLS) glass-ceramics. In total, 48 central incisor crowns (n = 12) were fabricated from IPS e.max CAD LT (IPS), Celtra Duo LT (CD), and GC Initial UHT zirconia (GC, GC1). A standard of 1.5 mm labial thickness of the crowns was determined for three groups (IPS, CD, GC), and 1 mm labial thickness was determined for GC1. The crowns’ translucency values were assessed in terms of the contrast ratio (CR). One-way ANOVA and Tamhane tests were used for analyzing the data. The mean CRs of GC1, GC, IPS, and CD specimens were 0.13 ± 0.01, 0.22 ± 0.01, 0.22 ± 0.04, and 0.29 ± 0.04, respectively. The CD group had significantly higher CR values than the other groups. The difference between the CR values of GC and IPS groups was not statistically significant. The GC1 group’s CR was significantly lower than the GC group. It is critical to select monolithic materials in order to achieve esthetic restorations, particularly for anterior teeth. The translucency of monolithic restorative materials was influenced by the type and the thickness of the material used. Full article
(This article belongs to the Special Issue Optical Technology in Dentistry)
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17 pages, 3498 KB  
Article
Impact of Thermomechanical Aging on Marginal Fit and Fracture Resistance of CAD/CAM Endocrowns Fabricated from Different Materials
by Bülent Kadir Tartuk and Gizem Akın Tartuk
Polymers 2026, 18(1), 143; https://doi.org/10.3390/polym18010143 - 5 Jan 2026
Viewed by 391
Abstract
The restoration of endodontically treated teeth remains a clinical challenge, particularly when substantial coronal tissue loss is present. Endocrowns fabricated using CAD/CAM technologies offer a conservative and esthetic alternative to conventional post-core systems; however, their long-term performance may be influenced by age-related mechanical [...] Read more.
The restoration of endodontically treated teeth remains a clinical challenge, particularly when substantial coronal tissue loss is present. Endocrowns fabricated using CAD/CAM technologies offer a conservative and esthetic alternative to conventional post-core systems; however, their long-term performance may be influenced by age-related mechanical and thermal stresses. This study evaluated the effect of thermomechanical aging on the marginal adaptation and fracture resistance of endocrowns fabricated from three CAD/CAM materials: zirconia-reinforced lithium silicate (ZLS), polyetherether ketone (PEEK), and 3D-printed resin. Sixty extracted human molars were endodontically treated and restored with endocrowns produced from these materials (n = 20 per group) and then subdivided into aged (n = 10) and control (n = 10) subgroups. Thermomechanical aging involved 5000 thermal cycles between 5 °C and 55 °C, and 75,000 mechanical loading cycles at 50 N. Marginal gaps were examined using scanning electron microscopy, and fracture resistance was tested under axial load at a crosshead speed of 0.5 mm/min. Data were analyzed using two-way ANOVA followed by Tukey’s post hoc test (α = 0.05). Thermomechanical aging significantly increased the marginal gaps in all materials (p < 0.05). The smallest marginal discrepancies were observed in the 3D-printed resin group, while the largest occurred in the ZLS after aging, likely due to dimensional changes during crystallization. Fracture resistance decreased in ZLS (−21.2%) and 3D resin (−20.9%) after aging (p < 0.05) but was not significantly affected in PEEK (−5.4%, p = 0.092). Thermomechanical aging adversely affects marginal adaptation across all materials, whereas its impact on strength is material-dependent. PEEK demonstrated the most stable mechanical performance and may represent a promising alternative for long-term endocrown restorations. Full article
(This article belongs to the Section Polymer Applications)
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13 pages, 1963 KB  
Article
Mitochondrial Genomes Reveal Population Structure of the Locust Oedaleus decorus (Orthoptera: Acrididae: Oedipodinae) in China
by Xi Li, Shiqian Feng, Na Risu, Lijun Gao, Oyunbayar Amanjol, Uuganbayar Chuluunbaatar, Na Muriga, Hongmei Li, Zhan Niyazbekov, Alua Rysbekova, Xiongbing Tu, Guangjun Wang and Undarmaa Davaasambuu
Agronomy 2025, 15(12), 2830; https://doi.org/10.3390/agronomy15122830 - 9 Dec 2025
Viewed by 303
Abstract
The locust Oedaleus decorus undergoes massive outbreaks and engages in round-trip migratory flights across northern China and Mongolia. However, its specific genetic structure remains poorly understood. In this study, we sequenced the complete mitochondrial genomes of 163 O. decorus individuals from 16 locations [...] Read more.
The locust Oedaleus decorus undergoes massive outbreaks and engages in round-trip migratory flights across northern China and Mongolia. However, its specific genetic structure remains poorly understood. In this study, we sequenced the complete mitochondrial genomes of 163 O. decorus individuals from 16 locations in northern China using high-throughput sequencing data and analyzed its population structure. The results showed that these mitochondrial genomes are 15,142 to 15,914 bp in sizes, with size variation attributed to A + T-rich regions in intergenic spacers. All 13 protein-coding genes exhibited conserved lengths across samples. The overall genetic differentiation between populations was small (Fst = 0.00843), with high gene flow (Nm = 29.40). Both genetic differentiation and DAPC analyses revealed significant genetic differentiation in the New Barag Left Banner (NBL) population compared to the Zhengxiangbai Banner (ZB), Taibus Banner (TP), Xianghuang Banner (XH), and Zhenglan Banner (ZL) populations. The phylogenetic tree and haplotype network suggest Hap_20 is presumably a relatively ancestral haplotype and all haplotypes were divided into two clades, and no population formed a distinct independent clade. Our findings indicate that the O. decorus population in North China exhibits mitochondrial subtype differentiation. The lack of difference in genetic structure across different regions in North China is consistent with a high level of migratory activity by O. decorus in the region. Full article
(This article belongs to the Section Pest and Disease Management)
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14 pages, 1374 KB  
Article
Fracture Resistance of Zirconia-Reinforced Lithium Silicate in Single Posterior Implant-Supported Crowns: An In Vitro Study
by Maria Dolores Gómez-Adrián, Pasquale Natale, Alberto Molina-Palomero, Ángel Vicente-Escuder, Julián Espinosa-Giménez, Blanca Gil-Marqués, Marcelino Pérez-Bermejo, Carolina Larrazabal-Morón, Javier Barberá-Millán and Lucía Miralles-Jordá
Dent. J. 2025, 13(12), 574; https://doi.org/10.3390/dj13120574 - 3 Dec 2025
Viewed by 421
Abstract
Background/Objectives: Zirconia-reinforced lithium silicate (ZLS) is a glass–ceramic that combines the translucency of lithium disilicate with the enhanced strength provided by dispersed zirconia crystals. Evidence on the mechanical behavior of ZLS implant-supported crowns remains limited. This study evaluated the fracture resistance of posterior [...] Read more.
Background/Objectives: Zirconia-reinforced lithium silicate (ZLS) is a glass–ceramic that combines the translucency of lithium disilicate with the enhanced strength provided by dispersed zirconia crystals. Evidence on the mechanical behavior of ZLS implant-supported crowns remains limited. This study evaluated the fracture resistance of posterior monolithic ZLS crowns and analyzed the influence of cement type and artificial aging. Methods: Forty ZLS crowns (Celtra™ Duo) were fabricated, cemented onto straight titanium abutments and assigned to four groups (n = 10) according to cement type (adhesive or self-adhesive) and aging (500,000 cycles at 150 N). Specimens underwent axial load-to-fracture testing using a universal testing machine. Data were analyzed with Student’s t-tests and Kruskal–Wallis tests (α = 0.05). Results: Mean fracture resistance was 1625.46 ± 340.02 N. Although adhesive cement showed higher mean values than self-adhesive cement, no statistically significant differences were found (p = 0.102). Artificial aging also produced no significant reduction in fracture resistance (p = 0.674). All groups exceeded the physiological posterior occlusal forces. Conclusions: Monolithic ZLS crowns cemented onto titanium abutments demonstrated high fracture resistance under axial loading. Within the limitations of this in vitro design, neither cement type nor mechanical aging significantly affected performance. These findings support the mechanical feasibility of ZLS for posterior implant-supported single crowns, although further studies including thermomechanical aging and oblique loading are required. Full article
(This article belongs to the Special Issue Dental Materials Design and Innovative Treatment Approach)
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9 pages, 1698 KB  
Brief Report
Pathogen Identification and Treatment of Trichoderma koningiopsis ZL01 Mycosis in Firefly Pygoluciola sp. (Coleoptera: Lampyridae)
by Yan-Hong Chen, Shi-Ling Wang, Fu-Xin Li, Lian-Bing Lin, Wei-Wei Li and Qi-Lin Zhang
Insects 2025, 16(12), 1193; https://doi.org/10.3390/insects16121193 - 23 Nov 2025
Viewed by 578
Abstract
The artificial breeding of fireflies is vital for supplementing natural populations. Unfortunately, mycosis is being observed with increasing frequency in the artificial breeding of fireflies, resulting in increased mortality. This study reports the identification of a microfungus that infects larval Pygoluciola sp., a [...] Read more.
The artificial breeding of fireflies is vital for supplementing natural populations. Unfortunately, mycosis is being observed with increasing frequency in the artificial breeding of fireflies, resulting in increased mortality. This study reports the identification of a microfungus that infects larval Pygoluciola sp., a species of semi-aquatic fireflies, during artificial breeding. Morphological and molecular analysis identified the fungi as Trichoderma koningiopsis (named as ZL01 strain). In addition, nystatin was selected out of five candidates as the optimal antifungal agent against T. koningiopsis ZL01, with a minimum inhibitory concentration of 25.00 μg/mL. Acute oral and contact in vivo toxicity tests on larval Pygoluciola sp. confirmed the safety of nystatin. Furthermore, compared to a Pygoluciola sp. larval population infected with T. koningiopsis ZL01, nystatin treatment increased the survival rate of larvae by twofold (spray administration) and threefold (drip administration) at the end of a nine-day artificial breeding experiment. These findings indicate that nystatin could be used as a potential antifungal agent to control mycosis in artificially bred fireflies. This study was the first to document the infection of semi-aquatic fireflies by pathogens and provide a corresponding treatment strategy. Full article
(This article belongs to the Section Insect Behavior and Pathology)
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12 pages, 1478 KB  
Article
Defining the Heart Rate Zone Corresponding to the Lactate Threshold in Colombian Paso Horses
by Angélica María Zuluaga-Cabrera, Guilherme Barbosa da Costa, Iván Darío Martinez and María Patricia Arias
Animals 2025, 15(22), 3308; https://doi.org/10.3390/ani15223308 - 17 Nov 2025
Viewed by 1151
Abstract
Colombian Paso horses (CPs) excel in gait competitions due to their endurance, speed, and precision, which demand a high level of cardiorespiratory fitness. However, their training regimes often lack scientific support, and few studies have linked physiological parameters to optimal training zones. This [...] Read more.
Colombian Paso horses (CPs) excel in gait competitions due to their endurance, speed, and precision, which demand a high level of cardiorespiratory fitness. However, their training regimes often lack scientific support, and few studies have linked physiological parameters to optimal training zones. This study aimed to estimate the aerobic lactate threshold (LTaer) using mathematical methods and to correlate it with heart rate (HR) zones and blood lactate. Eighteen CPs were evaluated and classified into trained (GT) and untrained (GD) groups. All animals underwent a field-based incremental exercise test (IET) with continuous HR monitoring and serial blood sampling for lactate, creatinine, BUN, AST, and CK analysis. LTaer was estimated using three methods: visual inspection, and fixed thresholds at 2 mmol/L (ZL2), and 4 mmol/L (ZL4). HR zones corresponding to each threshold were then calculated based on a maximum estimated HR of 220 bpm. The visual method placed LTaer in zone 2 for both groups. ZL2 located the threshold in zone 2 for GT and in zone 3 for GD, whereas ZL4 placed the threshold in zone 4 for both groups. Although no intergroup differences in lactate or HR were observed, intragroup differences emerged above 75% of HRmax, indicating exponential lactate accumulation. Biochemical parameters revealed significant pre- to post-exercise changes, but no differences between groups, suggesting a standardized workload. This is the first study to propose field-based prediction of LTaer in CPs using HR derived from wearable technologies, based on blood lactate and a standardized exercise test’s results. Correlating HR zones with lactate thresholds facilitates workload analysis in the field. Future studies should investigate the maximal lactate steady state (MLSS) in this breed. Full article
(This article belongs to the Section Animal Physiology)
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28 pages, 30126 KB  
Article
Reliability Inference for ZLindley Models Under Improved Adaptive Progressive Censoring: Applications to Leukemia Trials and Flood Risks
by Refah Alotaibi and Ahmed Elshahhat
Mathematics 2025, 13(21), 3499; https://doi.org/10.3390/math13213499 - 1 Nov 2025
Viewed by 301
Abstract
Modern healthcare and engineering both rely on robust reliability models, where handling censored data effectively translates into longer-lasting devices, improved therapies, and safer environments for society. To address this, we develop a novel inferential framework for the ZLindley (ZL) distribution under the improved [...] Read more.
Modern healthcare and engineering both rely on robust reliability models, where handling censored data effectively translates into longer-lasting devices, improved therapies, and safer environments for society. To address this, we develop a novel inferential framework for the ZLindley (ZL) distribution under the improved adaptive progressive Type-II censoring strategy. The proposed approach unifies the flexibility of the ZL model—capable of representing monotonically increasing hazards—with the efficiency of an adaptive censoring strategy that guarantees experiment termination within pre-specified limits. Both classical and Bayesian methodologies are investigated: Maximum likelihood and log-transformed likelihood estimators are derived alongside their asymptotic confidence intervals, while Bayesian estimation is conducted via gamma priors and Markov chain Monte Carlo methods, yielding Bayes point estimates, credible intervals, and highest posterior density regions. Extensive Monte Carlo simulations are employed to evaluate estimator performance in terms of bias, efficiency, coverage probability, and interval length across diverse censoring designs. Results demonstrate the superiority of Bayesian inference, particularly under informative priors, and highlight the robustness of HPD intervals over traditional asymptotic approaches. To emphasize practical utility, the methodology is applied to real-world reliability datasets from clinical trials on leukemia patients and hydrological measurements from River Styx floods, demonstrating the model’s ability to capture heterogeneity, over-dispersion, and increasing risk profiles. The empirical investigations reveal that the ZLindley distribution consistently provides a better fit than well-known competitors—including Lindley, Weibull, and Gamma models—when applied to real-world case studies from clinical leukemia trials and hydrological systems, highlighting its unmatched flexibility, robustness, and predictive utility for practical reliability modeling. Full article
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16 pages, 2738 KB  
Article
Response of Soil Organic Carbon and Microbial Metabolic Pathways in Guangxi Karst Regions to Different Vegetation Types
by Keye Zhu, Sheng Xu, Lei Wang, Siqi Wu, Wenxu Zhu, Nanyan Liao and Wuzheng Li
Forests 2025, 16(11), 1664; https://doi.org/10.3390/f16111664 - 30 Oct 2025
Viewed by 757
Abstract
This study investigates how different vegetation types influence the molecular structure and abundance of soil organic carbon (SOC), as well as their influence on microbial metabolic pathways and community composition. Soil samples were collected from four different sites: a woodland dominated by Drypetes [...] Read more.
This study investigates how different vegetation types influence the molecular structure and abundance of soil organic carbon (SOC), as well as their influence on microbial metabolic pathways and community composition. Soil samples were collected from four different sites: a woodland dominated by Drypetes perreticulata (DP), a woodland dominated by Horsfieldia hainanensis (HM), a Zea mays L. field (ZL), and a citrus reticulata orchard (CB). The molecular structure of soil organic carbon (SOC) was characterised using Fourier Transform Infrared (FTIR) spectroscopy, identifying aromatic carbon (ArC), polysaccharide carbon (PSC), alkyl carbon (AlkC), amine carbon (AmC), ether carbon (EtC), and olefin carbon (OleC). Our results indicated significant variations across vegetation types: DG exhibited a significantly higher ArC content, while maize fields showed lower PSC levels. To analyse the relationships between different samples, we employed principal component analysis (PCA), which revealed distinct organic carbon structures across vegetation types, with the forests (DG and HM) significantly differing from agricultural sites (ZL and CB). Additionally, the 16S V3_V4 region of soil bacteria was sequenced using high-throughput sequencing. We employed PICRUSt2 to predict microbial metabolic pathways, revealing consistent core metabolic functions across samples but significant variations in secondary metabolism, with HM samples exhibiting the most distinctive metabolic profiles. Redundancy analysis (RDA) further demonstrated that microbial metabolic pathway variation explained 55.66% of organic carbon structure variance. Key microbial taxa exhibited significant associations with specific carbon source types and functional pathways. These findings highlight the pivotal mechanisms by which different vegetation types regulate soil organic carbon structure and composition by driving changes in microbial metabolic traits and community assembly. This study provides a mechanistic basis for understanding the coupling between vegetation, microorganisms, and carbon cycling, offering significant guidance for optimising vegetation restoration strategies, enhancing soil carbon sequestration capacity, and advancing carbon management practices based on microbial regulation. Full article
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13 pages, 877 KB  
Article
Dose-Response Behavior of Dental Material Using General Kinetic Order and Lambert W Deconvolution Models in CW-OSL
by Ioanna K. Sfampa
Methods Protoc. 2025, 8(5), 112; https://doi.org/10.3390/mps8050112 - 1 Oct 2025
Cited by 1 | Viewed by 524
Abstract
The present study presents a comparative evaluation of two analytical deconvolution models applied to Optically Stimulated Luminescence (OSL) decay curves of zirconia-reinforced lithium silicate (ZLS), a glass-ceramic material with potential applications in accidental dosimetry. ZLS samples were subjected to beta irradiation and measured [...] Read more.
The present study presents a comparative evaluation of two analytical deconvolution models applied to Optically Stimulated Luminescence (OSL) decay curves of zirconia-reinforced lithium silicate (ZLS), a glass-ceramic material with potential applications in accidental dosimetry. ZLS samples were subjected to beta irradiation and measured under Continuous Wave OSL (CW-OSL) protocols. A comparative analysis is conducted between two deconvolution approaches—the General Order Kinetics (GOK) model and a master analytical equation based on the Lambert W function. The results imply that both models yield a linear dose-response behavior of the fast OSL component; however, the Lambert W approach offers simpler fitting with fewer parameters. The abovementioned findings demonstrate the methodological robustness of the Lambert W formalism and also confirm that ZLS is a promising dosimetric material, aligning with the goals of protocol development in material characterization. Full article
(This article belongs to the Special Issue Analytical Methods in Natural Sciences and Archaeometry)
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14 pages, 2759 KB  
Article
Genetic Diversity Analysis in Natural Chinese Holly Using ISSR and SCoT Markers
by Meng Liu, Huixue He, Baoxin Zhang, Jianfang Zuo, Wona Ding, Bingsong Zheng, Jiejie Jiao and Xiaofei Wang
Horticulturae 2025, 11(9), 1078; https://doi.org/10.3390/horticulturae11091078 - 6 Sep 2025
Viewed by 957
Abstract
The Chinese holly (Ilex chinensis Sims.), an evergreen tree species native to China, is distributed mainly in regions south of the Qinling Mountains and Huai River. This research aimed to characterize the molecular profiles and genetic relationships of 40 Chinese holly genotypes [...] Read more.
The Chinese holly (Ilex chinensis Sims.), an evergreen tree species native to China, is distributed mainly in regions south of the Qinling Mountains and Huai River. This research aimed to characterize the molecular profiles and genetic relationships of 40 Chinese holly genotypes via inter-simple sequence repeat (ISSR) and start codon targeted (SCoT) polymorphism markers. Genetic diversity analysis revealed that the ISSR markers detected 111 polymorphic bands from 13 primers, with a polymorphism rate of 88.10%. The analysis generated parameters such as the observed allele number (Na = 1.876), effective allele number (Ne = 1.461), Shannon’s information index (I = 0.271), and expected heterozygosity (H = 0.411). In comparison, the SCoT markers produced 65 polymorphic bands from the 6 primers, resulting in a 100% polymorphism rate, with Na = 2.000, Ne = 1.695, I = 0.393, and H = 0.575. Cluster analysis classified the 40 genotypes into two main clusters with genetic similarity coefficients of 0.69 (ISSR) and 0.55 (SCoT). The ISSR markers presented the greatest similarity between the ZSS and ZLS genotypes, whereas the ZZDH and ZWW genotypes presented lower similarity. Conversely, the SCoT markers identified ZZP and ZJDS as the most similar, with ZLJ and ZHX showing less similarity. These results provide a theoretical basis for hybrid breeding, germplasm innovation, and conservation strategies of Chinese holly in China. Full article
(This article belongs to the Special Issue Advances in Cultivation and Breeding of Woody Plants)
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23 pages, 1898 KB  
Article
FGF14 Peptide Derivative Differentially Regulates Nav1.2 and Nav1.6 Function
by Parsa Arman, Zahra Haghighijoo, Carmen A. Lupascu, Aditya K. Singh, Nana A. Goode, Timothy J. Baumgartner, Jully Singh, Yu Xue, Pingyuan Wang, Haiying Chen, Dinler A. Antunes, Marijn Lijffijt, Jia Zhou, Michele Migliore and Fernanda Laezza
Life 2025, 15(9), 1345; https://doi.org/10.3390/life15091345 - 25 Aug 2025
Viewed by 1397
Abstract
Voltage-gated Na+ channels (Nav) are the molecular determinants of action potential initiation and propagation. Among the nine voltage-gated Na+ channel isoforms (Nav1.1–Nav1.9), Nav1.2 and Nav1.6 are of particular interest because of their developmental expression profile throughout the central nervous system (CNS) [...] Read more.
Voltage-gated Na+ channels (Nav) are the molecular determinants of action potential initiation and propagation. Among the nine voltage-gated Na+ channel isoforms (Nav1.1–Nav1.9), Nav1.2 and Nav1.6 are of particular interest because of their developmental expression profile throughout the central nervous system (CNS) and their association with channelopathies. Although the α-subunit coded by each of the nine isoforms can sufficiently confer transient Na+ currents (INa), in vivo these channels are modulated by auxiliary proteins like intracellular fibroblast growth factor (iFGFs) through protein–protein interaction (PPI), and probes developed from iFGF/Nav PPI complexes have been shown to precisely modulate Nav channels. Previous studies identified ZL0177, a peptidomimetic derived from a short peptide sequence at the FGF14/Nav1.6 PPI interface, as a functional modulator of Nav1.6-mediated INa+. However, the isoform specificity, binding sites, and putative physiological impact of ZL0177 on neuronal excitability remain unexplored. Here, we used automated planar patch-clamp electrophysiology to assess ZL0177’s functional activity in cells stably expressing Nav1.2 or Nav1.6. While ZL0177 was found to suppress INa in both Nav1.2- and Nav1.6-expressing cells, ZL0177 elicited functionally divergent effects on channel kinetics that were isoform-specific and supported by differential docking of the compound to AlphaFold structures of the two channel isoforms. Computational modeling predicts that ZL0177 modulates Nav1.2 and Nav1.6 in an isoform-specific manner, eliciting phenotypically divergent effects on action potential discharge. Taken together, these results highlight the potential of PPI derivatives for isoform-specific regulation of Nav channels and the development of therapeutics for channelopathies. Full article
(This article belongs to the Special Issue Ion Channels and Neurological Disease: 2nd Edition)
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16 pages, 682 KB  
Review
Claudin18.2 as a Promising Therapeutic Target in Gastric Cancer
by Agata Poniewierska-Baran, Paulina Plewa, Zuzanna Żabicka and Andrzej Pawlik
Cells 2025, 14(16), 1285; https://doi.org/10.3390/cells14161285 - 19 Aug 2025
Cited by 3 | Viewed by 5700
Abstract
Claudin-18.2 (CLDN18.2) is an isoform of a tight junction protein and has emerged as a promising therapeutic target in gastric cancer (GC). CLDN18.2 is responsible for gastric homeostasis and protects epithelial cells from low pH conditions. Interestingly, CLDN18.2 expression is strictly restricted to [...] Read more.
Claudin-18.2 (CLDN18.2) is an isoform of a tight junction protein and has emerged as a promising therapeutic target in gastric cancer (GC). CLDN18.2 is responsible for gastric homeostasis and protects epithelial cells from low pH conditions. Interestingly, CLDN18.2 expression is strictly restricted to the stomach, making it an ideal tumor marker. This narrative review presents the characterization and role of claudin 18.2 (CLDN18.2) as a promising biomarker in GC and a target for clinical therapies, more specifically CLDN18.2-targeted drugs and therapies including mABs (e.g., Zolbetuximab, Osemitamab, ZL-1211), bsAB, and CAR-T cell-based immunotherapies. We also summarize numerous ongoing worldwide clinical trials that are evaluating CLDN18.2 as a target for GC treatment. What seems to be crucial is that preclinical and clinical data indicate their high efficacy and safety. Full article
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18 pages, 8192 KB  
Article
Microstructure, Mechanical Properties, and Tribological Behavior of Friction Stir Lap-Welded Joints Between SiCp/Al–Fe–V–Si Composites and an Al–Si Alloy
by Shunfa Xiao, Pinming Feng, Xiangping Li, Yishan Sun, Haiyang Liu, Jie Teng and Fulin Jiang
Materials 2025, 18(15), 3589; https://doi.org/10.3390/ma18153589 - 30 Jul 2025
Viewed by 775
Abstract
Aluminum matrix composites provide an ideal solution for lightweight brake disks, but conventional casting processes are prone to crack initiation due to inhomogeneous reinforcement dispersion, gas porosity, and inadequate toughness. To break the conventional trade-off between high wear resistance and low toughness of [...] Read more.
Aluminum matrix composites provide an ideal solution for lightweight brake disks, but conventional casting processes are prone to crack initiation due to inhomogeneous reinforcement dispersion, gas porosity, and inadequate toughness. To break the conventional trade-off between high wear resistance and low toughness of brake disks, this study fabricated a bimetallic structure of SiCp/Al–Fe–V–Si aluminum matrix composite and cast ZL101 alloy using friction stir lap welding (FSLW). Then, the microstructural evolution, mechanical properties, and tribological behavior of the FSLW joints were studied by XRD, SEM, TEM, tensile testing, and tribological tests. The results showed that the FSLW process homogenized the distribution of SiC particle reinforcements in the SiCp/Al–Fe–V–Si composites. The Al12(Fe,V)3Si heat-resistant phase was not decomposed or coarsened, and the mechanical properties were maintained. The FSLW process refined the grains of the ZL101 aluminum alloy through recrystallization and fragmented eutectic silicon, improving elongation to 22%. A metallurgical bond formed at the joint interface. Tensile fracture occurred within the ZL101 matrix, demonstrating that the interfacial bond strength exceeded the alloy’s load-bearing capacity. In addition, the composites exhibited significantly enhanced wear resistance after FSLW, with their wear rate reduced by approximately 40% compared to the as-received materials, which was attributed to the homogenized SiC particle distribution and the activation of an oxidative wear mechanism. Full article
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25 pages, 1380 KB  
Review
Redefining the Fight Against SCLC: Standards, Innovations, and New Horizons
by Marcel Kemper, Lea Elisabeth Reitnauer, Georg Lenz, Georg Evers and Annalen Bleckmann
Cancers 2025, 17(13), 2256; https://doi.org/10.3390/cancers17132256 - 7 Jul 2025
Viewed by 2607
Abstract
Background: Small cell lung cancer (SCLC) remains a highly aggressive malignancy with a poor prognosis. Despite multimodal standard therapies, most patients relapse within months, and second-line treatment options such as topotecan offer only limited benefit. Novel therapeutic strategies are therefore urgently needed. Methods: [...] Read more.
Background: Small cell lung cancer (SCLC) remains a highly aggressive malignancy with a poor prognosis. Despite multimodal standard therapies, most patients relapse within months, and second-line treatment options such as topotecan offer only limited benefit. Novel therapeutic strategies are therefore urgently needed. Methods: This narrative review is based on a selective literature search conducted via PubMed and ClinicalTrials.gov (last updated June 2025). Results: Emerging treatment strategies include bispecific T-cell engagers (e.g., tarlatamab), antibody-drug conjugates (ADCs) such as sacituzumab govitecan, DS-7300, and ZL-1310, as well as targeted therapies. Among these, tarlatamab has demonstrated improved survival outcomes with an acceptable safety profile and is poised to become the new second-line standard. In contrast, ADCs and targeted agents have shown only modest efficacy and have yet to deliver meaningful survival benefits, often accompanied by increased toxicity. Additionally, the identification of molecular subtypes of SCLC has revealed subtype-specific differences in treatment response. However, clinical translation is challenged by intratumoral heterogeneity, plasticity, and the lack of standardized diagnostic assays. Conclusions: While tarlatamab represents a major therapeutic advancement, other agents remain in early clinical development and require validation in large, randomized trials. The clinical implementation of molecular subtyping remains limited, though it holds promise for future personalized treatment approaches. Despite recent progress, SCLC continues to pose substantial therapeutic challenges, emphasizing the need for improved treatment strategies and validated predictive biomarkers. Full article
(This article belongs to the Special Issue Advances in Targeted Therapies in Cancer (2nd Edition))
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