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13 pages, 4655 KB  
Article
Characterisation of a Missense Variant of the Alström Syndrome Centrosome and Basal Body Associated Protein (ALMS1) Gene Associated with Cardiomyopathy Using Induced Pluripotent Stem Cells
by Tanushri Dargar, Alexandre Janin, Valérie Risson, Estèle Lafont, Camille Valla, Vincent Gache and Marie Abitbol
Genes 2026, 17(2), 227; https://doi.org/10.3390/genes17020227 - 11 Feb 2026
Abstract
Background/Objectives: Human induced pluripotent stem cell (hiPSC) models provide a unique platform for testing the effect of genomic variants identified in patients with inherited diseases. In Alström syndrome, a rare multisystem disorder mainly caused by nonsense mutations in the ALMS1 gene, patients often [...] Read more.
Background/Objectives: Human induced pluripotent stem cell (hiPSC) models provide a unique platform for testing the effect of genomic variants identified in patients with inherited diseases. In Alström syndrome, a rare multisystem disorder mainly caused by nonsense mutations in the ALMS1 gene, patients often present with infantile cardiomyopathy, retinal dystrophy, type 2 diabetes, and hearing loss in addition to obesity. These diverse clinical manifestations highlight the pleiotropic functions of ALMS1 in cellular processes such as ciliary signalling, cell cycle regulation, and tissue homeostasis. In cats, the ALMS1:c.7384G>C missense variant has been associated with cardiomyopathy in the absence of other symptoms of Alström syndrome, raising questions regarding the impact of this variant on cardiac pathology. Methods: To answer these questions, we generated an hiPSC line carrying the human ALMS1:c.10004G>C missense variant, homologous to the ALMS1:c.7384G>C feline variant, as well as an isogenic control, to investigate the impact of this variant on cardiomyocyte differentiation and function. Results: The introduction of the ALMS1:c.10004G>C variant in the homozygous state in hiPSCs resulted in a significant reduction in cardiomyocyte differentiation efficiency. However, the variant did not affect contractile frequency, sarcomere organisation, sarcomere length, or cardiomyocyte cell size. Together, these results suggest that while the ALMS1:c.10004G>C variant impairs cardiomyocyte differentiation, it does not disrupt the structural or functional properties of the hiPSC-derived cardiomyocytes that do form. Conclusions: We have generated and initiated the characterisation of the third ALMS1 mutant hiPSC line and the first line based on a missense variant, but further research is needed on its relevance in modelling ALMS1-related changes. Our results also support the previous recommendation not to use ALMS1:c.7384G>C for the selection of breeding cats until further data confirm its intrinsic pathogenicity. Full article
(This article belongs to the Special Issue Hereditary Traits and Diseases in Companion Animals)
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29 pages, 5968 KB  
Article
Mathematical Formulation of a Symmetry-Compact Three-Step Algorithm for Computing the Spatio-Temporal Generalized FitzHugh–Nagumo Equations
by Joshua Sunday, Ezekiel Olaoluwa Omole, Roseline Bosede Ogunrinde, Geoffrey Micah Kumleng, Olabode Oludare Bamisile and Olakunle Oluwaseyi Kayode
Symmetry 2026, 18(2), 324; https://doi.org/10.3390/sym18020324 - 10 Feb 2026
Abstract
This study presents the mathematical formulation of a symmetry-compact three-step algorithm (TSA) for the numerical computation of the spatio-temporal generalized FitzHugh–Nagumo equation (FHNE), a class of one-dimensional time-dependent initial-boundary value partial differential equations. The proposed symmetry-compact TSA is constructed using the Lagrange polynomial [...] Read more.
This study presents the mathematical formulation of a symmetry-compact three-step algorithm (TSA) for the numerical computation of the spatio-temporal generalized FitzHugh–Nagumo equation (FHNE), a class of one-dimensional time-dependent initial-boundary value partial differential equations. The proposed symmetry-compact TSA is constructed using the Lagrange polynomial as the basis function, yielding a structurally balanced and computationally compact formulation with an inherent symmetry that facilitates automatic step-size adaptation over the integration interval. The symmetry-compact nature of the formulation enhances numerical stability while maintaining a reduced computational footprint, thereby improving both accuracy and efficiency when compared with existing numerical schemes. Prior to the application of the TSA, the FHNE is discretized in space, resulting in a system of ordinary differential equations suitable for time integration. Rigorous analyses of the stability and convergence properties of the symmetry-compact TSA are carried out to establish the reliability and robustness of the method. The performance of the proposed algorithm is quantitatively assessed using absolute error, maximum error, root mean square error, and central processing unit time for selected spatio-temporal test cases of the FHNE. The numerical results and corresponding solution profiles clearly demonstrate that the symmetry-compact TSA delivers superior accuracy, enhanced computational efficiency, and improved stability characteristics relative to existing methods, particularly in the presence of stiffness and chaotic dynamics. Full article
(This article belongs to the Section Mathematics)
15 pages, 468 KB  
Article
AI Communication Tone and Consumer Judgment: The Role of Servant Perception in Behavioral Intentions
by John Yang
Behav. Sci. 2026, 16(2), 253; https://doi.org/10.3390/bs16020253 - 10 Feb 2026
Abstract
Artificial intelligence is increasingly embedded in service interactions, requiring users to form rapid social judgments about AI communicators based on limited linguistic and contextual cues. This research examines how AI communication tone shapes behavioral intentions through social cognitive processes of role construal and [...] Read more.
Artificial intelligence is increasingly embedded in service interactions, requiring users to form rapid social judgments about AI communicators based on limited linguistic and contextual cues. This research examines how AI communication tone shapes behavioral intentions through social cognitive processes of role construal and agency attribution. Drawing on politeness theory, formality research, and social cognition perspectives, two scenario-based experiments test whether formal versus casual tone influences responses via attitudes toward the tone and the AI, and how these effects depend on perceptions of AI as a servant-like social actor. Study 1 shows that tone effects are moderated by servant perception and that economic framing, specifically paid versus free access, functions as an antecedent of hierarchical role construal. Study 2 replicates these effects and demonstrates that interaction structure, one-way versus two-way communication, similarly shapes servant perception by signaling differential autonomy. Across both studies, formal tone is more effective when AI is construed as subordinate, whereas casual tone is less effective under hierarchical role frames. By identifying servant perception as a central social cognitive mechanism, this research advances understanding of human judgment and decision making in technology-mediated interactions and offers implications for AI communication design aligned with role expectations. Because both studies rely on U.S. consumers, the findings should be interpreted within cultural contexts characterized by relatively low power distance, where role expectations and hierarchy norms may differ from other cultural settings. Full article
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21 pages, 1948 KB  
Article
Liposomal Delivery of Macleaya cordata Extract Alleviates Bacterial Diarrhea Through Intestinal Barrier Restoration, Microbiota Remodeling, and Inhibition of Inflammatory Factor Release
by Rujia Xie, Siya Chen, Wangxia Peng, Xinlei Tang, Hui Su, Bozhi Zeng, Congcong Chen, Chengcheng Yi, Jianguo Zeng and Jing Yang
Pharmaceutics 2026, 18(2), 218; https://doi.org/10.3390/pharmaceutics18020218 - 9 Feb 2026
Viewed by 31
Abstract
Background/Objectives: To overcome bottlenecks in the application of Macleaya cordata extract (MCE) in veterinary traditional Chinese medicine, such as low bioavailability of its active ingredients, gastrointestinal irritation, and muscular toxicity, this study aimed to develop a liposomal nano-delivery system loaded with MCE [...] Read more.
Background/Objectives: To overcome bottlenecks in the application of Macleaya cordata extract (MCE) in veterinary traditional Chinese medicine, such as low bioavailability of its active ingredients, gastrointestinal irritation, and muscular toxicity, this study aimed to develop a liposomal nano-delivery system loaded with MCE (MCE-Lips) to achieve the core objective of “enhancing efficacy and reducing toxicity” and to explore its potential application and mechanism of action in treating bacterial diarrhea. Methods: MCE-Lips were prepared using the thin-film dispersion method, and their physicochemical properties—particle size, encapsulation efficiency, and drug loading capacity—were characterized. In vitro, cytotoxicity against skeletal muscle cells and NCM460 intestinal epithelial cells was evaluated using the CCK-8 assay. The release of lactate dehydrogenase (LDH) from skeletal muscle cells was measured with an LDH assay kit. The expression levels of inflammatory factors (TNF-α, IL-6, and IL-1β) in both cell types were determined through ELISA. A fluorescent probe was employed to assess cell membrane integrity. The effect of MCE-Lips on the expression of tight junction proteins (ZO-1, Occludin, and Claudin-5) was evaluated via immunofluorescence. Acute toxicity was examined through H&E staining. A bacterial diarrhea model was established using Escherichia coli in mice, and comprehensive safety and efficacy were assessed through hematological tests and gastrointestinal motility evaluation. Finally, untargeted metabolomics and 16S rRNA sequencing were utilized to investigate the underlying mechanisms of action. Results: The prepared MCE-Lips had an average particle size of 86.49 nm and a high encapsulation efficiency of 89.07%. In vitro experiments demonstrated that MCE-Lips significantly alleviated skeletal muscle cell damage, reduced LDH release (p < 0.05), and effectively inhibited the expression of inflammatory factors IL-6, TNF-α, and IL-1β (p < 0.05). In NCM460 cells, MCE-Lips exhibited a more pronounced inhibitory effect on LPS-induced release of TNF-α (p < 0.01), IL-6 (p < 0.0001), and IL-1β (p < 0.0001) and enhanced intestinal barrier function by upregulating the expression of tight junction proteins ZO-1 (p < 0.001), Occludin (p < 0.01), and Claudin-5 (p < 0.01). In the bacterial diarrhea model, MCE-Lips showed excellent anti-diarrheal efficacy (p < 0.01). Hematological analysis indicated no systemic toxicity. At the endocrine level, the high-dose group significantly reduced motilin (MTL) levels (p < 0.01), which slowed intestinal motility and prolonged chyme retention, thereby alleviating diarrhea symptoms. Mechanistic studies revealed that it acts by regulating the intestinal metabolic profile and microbial community structure, with Desulfovibrio, Enterococcus, and Streptococcus identified as key characteristic differential genera. Conclusions: For the first time, an MCE liposome nanoparticle system was constructed, and untargeted metabolomics combined with 16S rRNA sequencing were employed to elucidate its anti-diarrheal mechanism. MCE-Lips exerts excellent antibacterial diarrhea effects through multiple mechanisms, including direct cytoprotection and anti-inflammatory action, enhancement of the intestinal barrier, regulation of gut function, and remodeling of the gut microecology. This work provides a novel paradigm for plant-derived nano-anti-diarrheal agents. The systematic evaluation of the pharmacodynamics of MCE-Lips in a piglet bacterial diarrhea model will lay a solid foundation for its eventual market application. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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20 pages, 8956 KB  
Article
Construction of a Eukaryotic Algae-Specific Metagenomic Classification Database and Its Application to Tara Oceans Data
by Xubing Xie, Mingjiang Wu and Shengqin Wang
Diversity 2026, 18(2), 110; https://doi.org/10.3390/d18020110 - 9 Feb 2026
Viewed by 36
Abstract
Eukaryotic algae are key contributors to biodiversity and ecosystem functioning in aquatic environments. However, understanding their global diversity patterns and community assembly mechanisms remains limited by the lack of high-resolution, highly specific analytical methods. Here, we present the first eukaryotic algae-specific classification database, [...] Read more.
Eukaryotic algae are key contributors to biodiversity and ecosystem functioning in aquatic environments. However, understanding their global diversity patterns and community assembly mechanisms remains limited by the lack of high-resolution, highly specific analytical methods. Here, we present the first eukaryotic algae-specific classification database, EukAlgae-T (Eukaryotic Algae Taxonomic database), constructed based on single-copy orthologous genes. The database integrates 50,581 non-redundant marker genes from 479 high-quality genomes and was applied to analyze 939 marine metagenomic samples from the Tara Oceans project. Our results reveal that the genomically represented fraction of the global algal community is dominated by a widely distributed core taxonomic group, comprising 125 of the 230 detected species. Redundancy analysis indicated that community structure is primarily regulated by latitude and iron concentration on a global scale. In contrast, Mantel tests revealed strong regional heterogeneity, with temperature, salinity, and iron concentration acting as universal local drivers, albeit with varying effect sizes and combinations across ocean basins. Co-occurrence network analysis further demonstrated predominantly cooperative interactions among taxa, forming a highly modular and stable network structure, and identified key hub taxa characterized by low abundance but high connectivity. Together, this study provides a dedicated framework for eukaryotic algae metagenomic analysis and demonstrates that algal community assembly is driven by multi-scale environmental filtering: broadly constrained by climate zones and iron limitation at the global scale and regionally reshaped by local oceanographic processes (e.g., thermohaline structure). Cooperative coexistence and niche differentiation among taxa jointly underpin the maintenance of global algal diversity. Full article
(This article belongs to the Section Marine Diversity)
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27 pages, 1757 KB  
Article
Partial Serotonin Transporter Deficiency Modulates Plasma Metabolome, Arginine-Nitric Oxide Pathway and Emotional Behavior in Mice Exposed to Western Diet
by Anna Gorlova, Raymond Cespuglio, Angelika Schmitt-Böhrer, Alexey Deykin, Allan V. Kalueff, Ksenia Lebedeva, Andrey Nedorubov, Gabriela Ortega Shulte, Evgeniy Svirin, Aleksey Lyundup, Klaus-Peter Lesch and Tatyana Strekalova
Metabolites 2026, 16(2), 117; https://doi.org/10.3390/metabo16020117 - 9 Feb 2026
Viewed by 146
Abstract
Background/Objectives: Reduced serotonin transporter (SERT) function is associated with increased vulnerability to emotional and metabolic dysregulation, particularly in elderly women. Most preclinical studies relied on young male rodents with complete Sert deficiency; the Western diet (WD) acerbates these abnormalities. However, complete Sert [...] Read more.
Background/Objectives: Reduced serotonin transporter (SERT) function is associated with increased vulnerability to emotional and metabolic dysregulation, particularly in elderly women. Most preclinical studies relied on young male rodents with complete Sert deficiency; the Western diet (WD) acerbates these abnormalities. However, complete Sert loss does not fully reflect the human condition of partial SERT dysfunction. Here, we examined the effects of WD in aged female Sert+/− mice on metabolic, biochemical, molecular, and behavioral outcomes. Methods: Wild-type (WT) and Sert+/− mice were fed WD or a control diet. Emotionality, cognition, glucose tolerance (GT), plasma 1HNMR spectroscopy metabolome and biochemical parameters were studied. Gene expression analyses of nitric oxide (NO)-related markers were performed in the hypothalamus, dorsal raphe, and liver. Results: WD-exposed WT mice showed impaired GT and reduced plasma lactate and branched-chain amino acid levels; metabolome changes were more pronounced in mutants, while GT was unchanged. Naïve Sert+/− mice exhibited lower lactate and alanine levels compared with WT controls. WD increased leptin and cholesterol levels in both genotypes, whereas triglyceride concentrations were reduced in Sert+/− mice. Both WD and Sert deficiency increased Nos expression, while arginase expression was differentially regulated by genotype and diet. Malondialdehyde levels were elevated in the prefrontal cortex of Sert+/− mice regardless diet. WD also impaired object recognition memory and induced anxiety- and depression-like behaviors, with more pronounced effects in Sert+/− mice, except marble test behavior. Conclusions: Partial Sert deficiency aggravates some but not all WD-induced metabolic alterations, enhances oxidative stress, dysregulates arginine–NO signaling, and modifies behavior, highlighting the translational relevance of Sert+/− mice for modeling SERT dysfunction. Full article
(This article belongs to the Special Issue Metabolomics in Human Diseases and Health: 2nd Edition)
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25 pages, 1909 KB  
Article
Preliminary Study on Sexual Maturation Pattern of Shenxian Pigs and Molecular Characteristics of Sexual Precocity in Boars
by Jialong Zhao, Shan Yang, Haitao Chen, Yu Li, Jiahui Yuan, Mingxin Sun, Chunlian Lu and Hongzhan Cao
Int. J. Mol. Sci. 2026, 27(4), 1663; https://doi.org/10.3390/ijms27041663 - 9 Feb 2026
Viewed by 73
Abstract
This study aimed to determine the sexual maturation pattern of Shenxian pigs by combining observation, teaser boar testing, and back-pressure methods, and to apply this pattern for early breeding to shorten the generation interval and increase production efficiency. Subsequently, high-throughput transcriptome technology was [...] Read more.
This study aimed to determine the sexual maturation pattern of Shenxian pigs by combining observation, teaser boar testing, and back-pressure methods, and to apply this pattern for early breeding to shorten the generation interval and increase production efficiency. Subsequently, high-throughput transcriptome technology was used to compare gene expression levels in testicular tissues of Shenxian pigs before and after sexual maturity, as well as between sexually mature Shenxian pigs and Shenxian × Large White crossbred pigs. Functional analysis of differentially expressed genes (DEGs) was conducted to screen candidate genes related to sexual maturation and precocity in Shenxian pigs. The results showed that boars reached sexual maturity at an average age of 116 days in winter and 129 days in summer. For sows, the first estrus occurred at 114 days, the second at 134 days, and the third at 154 days in winter; corresponding ages in summer were 125, 144, and 164 days, respectively. The duration of estrus was around 3 days, and the estrus interval was approximately 20 days for both seasons. Comparative trials revealed no significant change in production performance when selection and first mating were conducted at 5 months of age compared to previous practices. Transcriptome sequencing of testicular tissues before and after sexual maturity in Shenxian pigs identified 6016 upregulated genes, primarily associated with reproduction and sperm function, influencing sexual maturation. The comparison between sexually mature Shenxian pigs and crossbred pigs identified 582 upregulated genes, mainly involved in hormone synthesis, affecting the onset of puberty in Shenxian pigs. After intersecting and functionally analyzing the upregulated genes from both sets, SRD5A1 and CYP11B2 were selected as the most likely candidate genes to affect precocious puberty in Shenxian pigs. Full article
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12 pages, 592 KB  
Review
Pistachio Allergy: Integrating Molecular Diagnostics and Clinical Phenotypes
by Julia Tworowska, Ola Sobieska-Poszwa and Agnieszka Kowalczyk
Diagnostics 2026, 16(4), 513; https://doi.org/10.3390/diagnostics16040513 - 9 Feb 2026
Viewed by 125
Abstract
Background: Pistachio allergy is an increasingly recognized form of tree nut allergy and is strongly associated with cashew allergy due to pronounced molecular cross-reactivity. Despite its relatively low prevalence in the general population, pistachio allergy may result in severe systemic reactions and represents [...] Read more.
Background: Pistachio allergy is an increasingly recognized form of tree nut allergy and is strongly associated with cashew allergy due to pronounced molecular cross-reactivity. Despite its relatively low prevalence in the general population, pistachio allergy may result in severe systemic reactions and represents a significant diagnostic challenge, particularly in polysensitized patients. Objective: This narrative review aims to critically evaluate current diagnostic approaches to pistachio allergy, with a focus on molecular allergen components, mechanisms of cross-reactivity, clinical phenotypes, and the added value of advanced diagnostic tools for risk stratification. Methods: A narrative synthesis of the literature was conducted, integrating data from population-based studies, clinical cohorts, component-resolved diagnostics, basophil activation testing, and oral food challenge studies. Emphasis was placed on the diagnostic performance and clinical utility of extract-based versus molecular and functional assays. Results: Pistachio allergy is predominantly associated with sensitization to seed storage proteins, including 2S albumins, 7S vicilins, and 11S legumins, which share high sequence and structural homology with corresponding cashew allergens. This molecular relationship underlies frequent co-sensitization and clinical co-reactivity. Conventional extract-based tests show limited specificity, whereas component-resolved diagnostics and functional assays improve diagnostic precision, facilitate phenotype-based risk stratification, and may reduce the need for oral food challenges in selected patients. Conclusions: Accurate diagnosis of pistachio allergy requires an integrated approach combining clinical history with molecular and functional diagnostics. Incorporation of component-resolved diagnostics and basophil activation testing into diagnostic algorithms allows improved differentiation between asymptomatic sensitization and clinically relevant allergy, supporting individualized patient management and safer clinical decision-making. Full article
(This article belongs to the Special Issue Allergy and Asthma: Clinical Diagnostics and Management)
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15 pages, 8531 KB  
Article
Simufilam in Alzheimer’s Disease: Assessment of Efficacy of a Controversial Drug in Human Neuronal Cell Culture
by Ankita Srivastava, Heather A. Renna, Tahmina Hossain, Thomas Palaia, Aaron Pinkhasov, Irving H. Gomolin, Joshua De Leon, Thomas Wisniewski and Allison B. Reiss
Pharmaceuticals 2026, 19(2), 281; https://doi.org/10.3390/ph19020281 - 7 Feb 2026
Viewed by 195
Abstract
Background/Objectives: Alzheimer’s disease (AD) is a progressive multifactorial neurodegenerative disorder. Current AD therapies offer minimal benefits and do not prevent or repair neuronal damage. More effective therapeutic approaches are needed to restore normal bioenergetics and metabolic function to AD neurons. Simufilam is [...] Read more.
Background/Objectives: Alzheimer’s disease (AD) is a progressive multifactorial neurodegenerative disorder. Current AD therapies offer minimal benefits and do not prevent or repair neuronal damage. More effective therapeutic approaches are needed to restore normal bioenergetics and metabolic function to AD neurons. Simufilam is a small-molecule oral drug that targets filamin A, a scaffolding protein in brain cells. Phase III clinical trials of simufilam failed to show any significant cognitive or functional improvements in AD patients. The purpose of this study is to identify and explain the molecular mechanisms that may have contributed to this drug’s lack of clinical success. Methods: Our study investigates the effects of simufilam on amyloid processing, neuronal health, and mitochondrial functioning in the SH-SY5Y human neuronal cell model. SH-SY5Y cells were differentiated into neurons using 10 µM retinoic acid. Undifferentiated and differentiated SH-SY5Y were exposed to simufilam (5 µM, 50 µM; 24 hr). Results: Simufilam did not affect the expression of genes involved in amyloid processing. Amyloid precursor protein (APP), β-secretase, and α-secretase mRNA levels in simufilam-treated SH-SY5Y cells were all unchanged compared to untreated cells. However, amyloidogenic β-secretase protein was significantly increased (fold change 1.17) at 50 µM of simufilam only in differentiated SH-SY5Y cells without affecting APP or α-secretase protein expression. Simufilam at the 50 µM concentration reduced brain-derived neurotrophic factor protein levels (fold change 0.7) only in differentiated SH-SY5Y. Further, simufilam did not improve mitochondrial genes or structure. Conclusions: Our results align with clinical outcomes and indicate that insufficient activity across multiple tests of ability to impact processes related to neuronal health can serve as a preliminary indicator of limited clinical utility. Full article
(This article belongs to the Special Issue Pharmacotherapy for Alzheimer’s Disease, 2nd Edition)
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15 pages, 4969 KB  
Article
Mechanical Response and Functional Performance of Heat-Treated LPBF NiTi Shape Memory Alloys
by Jerzy Ratajski, Błażej Bałasz, Agnieszka Peła, Paweł Krupski, Kamil Bochenk, Michał Tacikowski and Łukasz Major
Materials 2026, 19(3), 627; https://doi.org/10.3390/ma19030627 - 6 Feb 2026
Viewed by 111
Abstract
This study evaluates how solution treatment and aging influence the deformation mechanisms, phase transformations and functional performance of NiTi alloys produced by laser powder bed fusion (LPBF). Tensile tests performed at room temperature (RT) and −20 °C (LT) were combined with Differential Scanning [...] Read more.
This study evaluates how solution treatment and aging influence the deformation mechanisms, phase transformations and functional performance of NiTi alloys produced by laser powder bed fusion (LPBF). Tensile tests performed at room temperature (RT) and −20 °C (LT) were combined with Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD) and Transmission Electron Microscopy (TEM) analyses to correlate mechanical response with transformation thermodynamics and microstructural evolution. In the as-fabricated (AF) condition, deformation is governed by twinning and martensitic plasticity due to suppressed stress-induced martensite (SIM). Solution treatment (ST) restores reversible SIM at RT and preserves partial recoverability at LT as a result of microstructural homogenization and internal stress relief. Aging at 500 °C (A1h, A20h) promotes Ni4Ti3 precipitation, increasing transformation temperatures and stabilizing martensite, which leads to entirely irreversible deformation at both temperatures. These findings establish a clear functional continuum—ranging from recoverable (ST) to dissipative (AF) and fully irreversible (A20h) behavior—and provide a mechanistic framework for tailoring LPBF NiTi components for actuators, energy-storage and energy-dissipation applications. Full article
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22 pages, 1463 KB  
Article
Diagnostic Role of Chromatic Full-Field Stimulus Test in Rod–Cone Versus Cone Dystrophies
by Aykut Demirkol, Esra Sahli, Baichun Hou, Promie R. Faruque, Ilay Demirkol, Kuzey Soydas and Stephen H. Tsang
Biomedicines 2026, 14(2), 377; https://doi.org/10.3390/biomedicines14020377 - 6 Feb 2026
Viewed by 201
Abstract
Background: Inherited retinal dystrophies are a heterogeneous group of progressive disorders impacting photoreceptor function, often limiting the usefulness of standard electroretinography in advanced cases. Full-field stimulus test (FST) testing has become a sensitive psychophysical technique for detecting residual visual function when traditional electrophysiology [...] Read more.
Background: Inherited retinal dystrophies are a heterogeneous group of progressive disorders impacting photoreceptor function, often limiting the usefulness of standard electroretinography in advanced cases. Full-field stimulus test (FST) testing has become a sensitive psychophysical technique for detecting residual visual function when traditional electrophysiology is non-recordable. This study evaluated the ability of chromatic FST to differentiate rod–cone from cone photoreceptor dysfunction in patients with genetically confirmed inherited retinal dystrophies. Methods: Cross-sectional FST data were analyzed from 39 patients (mean age 45.7 ± 20.0 years) with genetically confirmed inherited retinal dystrophies at a tertiary academic center. All participants underwent standardized FST testing using white, red, and blue stimuli. Patients were classified into rod–cone dystrophy (n = 27) or cone dystrophy (n = 12) groups based on genetic and clinical criteria. Group comparisons focused on FST thresholds and especially blue–red threshold differences as markers of photoreceptor-mediated function. Bonferroni correction was applied to adjust for multiple comparisons across four primary FST parameters. Additional analyses by genotype were performed with nonparametric tests. Results: Eight different genetic mutations were represented, including Phosphodiesterase 6A (PDE6A) (n = 10), Rhodopsin (RHO) (n = 7), Phosphodiesterase 6B (PDE6B) (n = 6), Cyclic Nucleotide-Gated Channel Beta 1 (CNGB1) (n = 4), Cyclic Nucleotide-Gated Channel Alpha 3 (CNGA3) (n = 4), Nuclear Receptor Subfamily 2 Group E Member 3 (NR2E3) (n = 4), Guanylate Cyclase 2D (GUCY2D) (n = 2), and Cyclic Nucleotide-Gated Channel Beta 3 (CNGB3) (n = 2). Blue–red FST threshold differences exhibited moderate group discrimination in uncorrected analysis, with rod–cone dystrophies averaging −8.35 ± 10.37 dB and cone dystrophies −11.20 ± 14.60 dB. The area under the receiver operating characteristic curve for blue–red difference was 0.74 (95% CI: 0.59–0.90), with 75% sensitivity and 70.4% specificity at a −10 dB cutoff. However, no chromatic FST parameter maintained statistical significance between groups after Bonferroni correction. Inter-eye FST correlation was high (r = 0.758, p < 0.001), supporting test reliability. Conclusions: Chromatic FST testing provides a practical and sensitive means to assess photoreceptor function in advanced inherited retinal dystrophies, particularly when standard electrophysiologic methods are uninformative. Although the blue–red threshold difference offers moderate discrimination between rod–cone and cone dystrophies in uncorrected analysis, no chromatic parameter reached statistical significance after adjustment for multiple testing. Chromatic FST should be considered a supplementary approach for clinical monitoring and therapeutic studies in advanced retinal dystrophies, with further validation needed in larger cohorts. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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20 pages, 44649 KB  
Article
Multi-Omic and Spatial Profiling Identifies an Epithelial DKK1 Associated with Microenvironmental Remodeling in Pancreatic Ductal Adenocarcinoma
by Jiajia Xu, Kaiqiang Qian, Yanyu Ding, Jianghao Cheng, Xu Zhang, Yong Huang and Bo Liu
Curr. Issues Mol. Biol. 2026, 48(2), 182; https://doi.org/10.3390/cimb48020182 - 5 Feb 2026
Viewed by 121
Abstract
Objective: This study aimed to identify clinically relevant regulators of pancreatic ductal adenocarcinoma (PDAC), a disease characterized by stromal remodeling and immune suppression, and to define their links to malignant progression and microenvironmental reprogramming. Methods: We integrated multi-cohort bulk, single-cell, and spatial transcriptomic [...] Read more.
Objective: This study aimed to identify clinically relevant regulators of pancreatic ductal adenocarcinoma (PDAC), a disease characterized by stromal remodeling and immune suppression, and to define their links to malignant progression and microenvironmental reprogramming. Methods: We integrated multi-cohort bulk, single-cell, and spatial transcriptomic datasets and subsequently validated bulk differential expression and network analyses with machine learning-based prioritization in an independent combined cohort (TCGA-PAAD plus GSE62452). Single-cell mapping was used to assess cell-type specificity, positioning candidates along inferCNV- and pseudotime-defined malignant continua. In Visium sections, a DKK1-associated program score quantified intratumoral spatial heterogeneity and informed our analyses of ligand–receptor communication. Bulk immune deconvolution linked gene levels to immune infiltration patterns, and functional assays were used to test the impact of DKK1 knockdown on migration, proliferation, clonogenic growth, and apoptosis in PDAC cells. Results: Four reproducible tumor-associated genes—DKK1, COL10A1, SULF1, and SLC24A3—were prioritized and validated externally. DKK1 was predominantly expressed by epithelial tumor cells and tracked along a malignant progression continuum. Spatially, the DKK1 program localized to epithelial-dominant regions, revealed pronounced intratumoral heterogeneity, and highlighted epithelial–endothelial and endothelial–immune signaling in high-score areas. Immune deconvolution associated higher DKK1 expression with increased myeloid infiltration and reduced cytotoxic lymphocyte signatures. Functionally, DKK1 knockdown impaired migration, proliferation, and clonogenicity while increasing apoptosis. Conclusions: We demonstrate that DKK1 is an epithelial-derived regulator linked to malignant progression and tumor–stroma–immune remodeling, supporting its potential as a biomarker and therapeutic target in PDAC treatment, including rational combinations with stroma-modulating strategies and immunotherapy. Full article
(This article belongs to the Special Issue Linking Genomic Changes with Cancer in the NGS Era, 3rd Edition)
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21 pages, 2775 KB  
Article
Comparative Genomics Reveals Host-Specific Adaptation of Pyricularia oryzae Strains Isolated from Rice and Barnyard Grass
by Wenda Sun, Xiaohan Zhang, Zhuan Zhang, Xiaofang Xie, Song Tang, Tian Song, Baoxu Lu, Jiafeng Wang, Zhibin Liang, Xiaofan Zhou and Yizhen Deng
J. Fungi 2026, 12(2), 109; https://doi.org/10.3390/jof12020109 - 5 Feb 2026
Viewed by 193
Abstract
Barnyard grass, a widespread and persistent weed in rice paddies, belongs to the same family as rice and may act as a bridge host for the rice blast fungus. This study utilized comparative genomics to analyze six Pyricularia oryzae strains isolated from barnyard [...] Read more.
Barnyard grass, a widespread and persistent weed in rice paddies, belongs to the same family as rice and may act as a bridge host for the rice blast fungus. This study utilized comparative genomics to analyze six Pyricularia oryzae strains isolated from barnyard grass (Baicao series) and rice (GDYJ7 and ZJX18), integrating pathogenicity assays, whole-genome sequencing, and functional annotation. Pathogenicity tests demonstrated host specificity, as Baicao series strains caused typical lesion symptoms on barnyard grass but not on rice leaves, while GDYJ7 and ZJX18 caused lesions mainly on rice. Genomic analyses indicated that Baicao series strains possessed larger genomes (41.04 Mb to 41.16 Mb) with a higher content of repetitive sequences (6.68% to 7.09%) compared to rice strains GDYJ7 and ZJX18 (38.69 Mb and 39.05 Mb; 3.66% and 3.71% repeats). Phylogenetic analysis confirmed that Baicao series strains represent a grass-infecting pathotype of P. oryzae species, as they were grouped with the established grass-isolated P. oryzae strains, while GDYJ7 and ZJX18 were grouped with rice-isolated P. oryzae strains. However, Baicao series, GDYJ7 and ZJX18 are all relatively distant from P. grisea species. PCR amplification revealed that Baicao series strains harbored significantly fewer avirulence genes (Avr-Pib, Avr-Pizt, PWL3) than GDYJ7 and ZJX18 (Avr-Pib, Avr-Pizt, Avr-Pi9, Avr-Pik, PWL2), with Baicao9 retaining only Avr-Pib. In summary, our results suggested that the genomic sequences of the barnyard grass-isolated strains serve as a valuable resource for the study of P. oryzae strains with differential host preference and provide novel insights into the evolution of pathogen genomes during host adaptation. Full article
(This article belongs to the Section Fungal Genomics, Genetics and Molecular Biology)
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17 pages, 912 KB  
Review
Fifth-Order Block Hybrid Approach for Solving First-Order Stiff Ordinary Differential Equations
by Ibrahim Mohammed Dibal and Yeak Su Hoe
AppliedMath 2026, 6(2), 21; https://doi.org/10.3390/appliedmath6020021 - 5 Feb 2026
Viewed by 163
Abstract
This study introduces a novel single-step hybrid block method with three intra-step points that attains fifth-order accuracy, offering an accurate and computationally economical tool for solving first-order differential equations. The method is specifically designed to handle first-order differential equations with efficiency and precision [...] Read more.
This study introduces a novel single-step hybrid block method with three intra-step points that attains fifth-order accuracy, offering an accurate and computationally economical tool for solving first-order differential equations. The method is specifically designed to handle first-order differential equations with efficiency and precision while employing a constant step size throughout the computation. To further enhance accuracy, interpolation techniques are incorporated to approximate function values at specific positions, addressing the fundamental properties of the method and verifying its mathematical soundness. These analyses confirm that the scheme satisfies the essential requirements of stability, consistency, and convergence, ensuring reliability in practical applications. In addition, the method demonstrates strong adaptability, making it suitable for a broad spectrum of problem settings that involve both stiff and non-stiff systems. Numerical experiments are carried out, and the results consistently demonstrate that the proposed method is robust and effective under various test cases. The outcomes further reveal that it frequently outperforms several existing numerical approaches in terms of both accuracy and computational efficiency. Full article
(This article belongs to the Section Computational and Numerical Mathematics)
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18 pages, 653 KB  
Article
Urban Adaptation to Climate Change: Climate Refuge Networks as a Strategy to Mitigate Thermal Stress
by Carmen Díaz-López, Rubén Mora-Esteban, Francisco Conejo-Arrabal and Juan Marcos Castro-Bonaño
Urban Sci. 2026, 10(2), 100; https://doi.org/10.3390/urbansci10020100 - 4 Feb 2026
Viewed by 152
Abstract
Urban areas face rising risks from extreme heat due to climate change, intensifying thermal stress and exacerbating social inequalities. Urban climate refuges—cool, accessible indoor and outdoor public spaces that maintain their ordinary functions—are increasingly adopted as a local adaptation measure to protect vulnerable [...] Read more.
Urban areas face rising risks from extreme heat due to climate change, intensifying thermal stress and exacerbating social inequalities. Urban climate refuges—cool, accessible indoor and outdoor public spaces that maintain their ordinary functions—are increasingly adopted as a local adaptation measure to protect vulnerable populations during heat events. This study aims to develop and test a SWOT–CAME analytical framework to evaluate and compare the maturity, equity, and implementation logic of urban climate refuge networks in three European cities with contrasting climates and governance traditions: Barcelona, Amsterdam, and Copenhagen. A qualitative multiple-case design is combined with a transparent indicator set (coverage, accessibility, and typology mix) derived from official municipal sources and planning documents. Results show differentiated pathways: Barcelona represents an institutionalized network model; Amsterdam illustrates an emerging coordinated public-health approach; and Copenhagen reflects an ecosystem-based orientation where green–blue infrastructure provides substantial passive cooling capacity but requires clearer heat-specific operational protocols. The discussion highlights the need for hybrid adaptation strategies that combine nature-based solutions with operational governance and targeted support for vulnerable groups. The paper concludes with a transferable framework for cities seeking to integrate climate refuges into resilience and climate-justice agendas. Full article
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