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36 pages, 2310 KB  
Review
Unpacking the Tumor Protein D52-like Family: Roles in Intracellular Trafficking and Cancer Progression
by Emma L. Dorward, Michael Ortiz, Claire M. Weekley, Kay K. Myo Min, Pascal H. G. Duijf, S. George Barreto, Michael W. Parker and Claudine S. Bonder
Cells 2026, 15(3), 252; https://doi.org/10.3390/cells15030252 (registering DOI) - 28 Jan 2026
Abstract
There is growing evidence that dysregulation of vesicle-mediated intracellular trafficking pathways leads to the development of various diseases, including cancer. Cancer exploits the intracellular trafficking pathways to modulate the protein flow, alter cell surface protein expression, and drive the hallmarks of cancer progression, [...] Read more.
There is growing evidence that dysregulation of vesicle-mediated intracellular trafficking pathways leads to the development of various diseases, including cancer. Cancer exploits the intracellular trafficking pathways to modulate the protein flow, alter cell surface protein expression, and drive the hallmarks of cancer progression, such as sustained proliferation signaling and evading immune surveillance. As such, there is increasing interest in understanding the proteins that regulate these processes to better understand cancer biology and to identify novel ways to hinder disease progression. A group of small proteins, known as the Tumor Protein D52 (TPD52)-like family, has been identified and is increasingly recognized for its roles in intracellular trafficking within cancer cells. This family consists of four members: TPD52, TPD53, TPD54, and TPD55. Herein, we review the current literature on the TPD52-like family in cancer and detail the current known cellular functions (e.g., intracellular trafficking roles, lipid biogenesis, cell proliferation, and cell cycle regulation). Overexpression of family members, notably TPD52 and TPD54, has been heavily implicated in tumorigenic roles such as cell migration, invasion, proliferation, and protein–protein interactions. Additionally, there is mounting evidence that this family also has isoform-specific and/or tissue-specific functions, which is of clinical interest. A better understanding of the mechanistic actions of this protein family holds the promise of identifying novel therapeutic targets that exploit the broader multi-target nature of intracellular trafficking regulators to disrupt oncogenic processes. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Tumor Pathogenesis)
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49 pages, 7642 KB  
Article
Neuro-Geometric Graph Transformers with Differentiable Radiographic Geometry for Spinal X-Ray Image Analysis
by Vuth Kaveevorayan, Rapeepan Pitakaso, Thanatkij Srichok, Natthapong Nanthasamroeng, Chutchai Kaewta and Peerawat Luesak
J. Imaging 2026, 12(2), 59; https://doi.org/10.3390/jimaging12020059 (registering DOI) - 28 Jan 2026
Abstract
Radiographic imaging remains a cornerstone of diagnostic practice. However, accurate interpretation faces challenges from subtle visual signatures, anatomical variability, and inter-observer inconsistency. Conventional deep learning approaches, such as convolutional neural networks and vision transformers, deliver strong predictive performance but often lack anatomical grounding [...] Read more.
Radiographic imaging remains a cornerstone of diagnostic practice. However, accurate interpretation faces challenges from subtle visual signatures, anatomical variability, and inter-observer inconsistency. Conventional deep learning approaches, such as convolutional neural networks and vision transformers, deliver strong predictive performance but often lack anatomical grounding and interpretability, limiting their trustworthiness in imaging applications. To address these challenges, we present SpineNeuroSym, a neuro-geometric imaging framework that unifies geometry-aware learning and symbolic reasoning for explainable medical image analysis. The framework integrates weakly supervised keypoint and region-of-interest discovery, a dual-stream graph–transformer backbone, and a Differentiable Radiographic Geometry Module (dRGM) that computes clinically relevant indices (e.g., slip ratio, disc asymmetry, sacroiliac spacing, and curvature measures). A Neuro-Symbolic Constraint Layer (NSCL) enforces monotonic logic in image-derived predictions, while a Counterfactual Geometry Diffusion (CGD) module generates rare imaging phenotypes and provides diagnostic auditing through counterfactual validation. Evaluated on a comprehensive dataset of 1613 spinal radiographs from Sunpasitthiprasong Hospital encompassing six diagnostic categories—spondylolisthesis (n = 496), infection (n = 322), spondyloarthropathy (n = 275), normal cervical (n = 192), normal thoracic (n = 70), and normal lumbar spine (n = 258)—SpineNeuroSym achieved 89.4% classification accuracy, a macro-F1 of 0.872, and an AUROC of 0.941, outperforming eight state-of-the-art imaging baselines. These results highlight how integrating neuro-geometric modeling, symbolic constraints, and counterfactual validation advances explainable, trustworthy, and reproducible medical imaging AI, establishing a pathway toward transparent image analysis systems. Full article
(This article belongs to the Special Issue Advances in Machine Learning for Medical Imaging Applications)
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16 pages, 39433 KB  
Article
Hidden Xyloglucan Architecture of the Pollen Intine in Gagea lutea Revealed by Sequential Enzymatic Unmasking
by Małgorzata Kapusta, Magdalena Narajczyk and Bartosz J. Płachno
Biology 2026, 15(3), 243; https://doi.org/10.3390/biology15030243 (registering DOI) - 28 Jan 2026
Abstract
The organisation of hemicelluloses within the pollen intine of many monocots remains inadequately characterised, partly due to the masking of epitopes within complex wall matrices. In this study, mature pollen grains of Gagea lutea (L.) Ker-Gawl. were analysed using immunofluorescence and immunogold technique [...] Read more.
The organisation of hemicelluloses within the pollen intine of many monocots remains inadequately characterised, partly due to the masking of epitopes within complex wall matrices. In this study, mature pollen grains of Gagea lutea (L.) Ker-Gawl. were analysed using immunofluorescence and immunogold technique with a variety of monoclonal antibodies that target xyloglucan (LM15, LM24, LM25, CCRC-M48), heteroxylan (LM10, LM11), heteromannan (LM21, LM22), and xylan (CCRC-M138). Semithin sections of LR White were examined both untreated and following a sequential enzymatic pretreatment, which included alkaline de-esterification followed by treatment with pectate lyase (RbPel1A) and endo-β-mannanase 5A. In untreated pollen, xyloglucan-related epitopes were identified within the intine, accompanied by additional intracellular labelling for LM15, and LM25; while for LM24 signal was only to the intine ring. Conversely, CCRC-M48 exhibited a more punctate distribution. Neither xylan- nor mannan-related epitopes were detected in the wall or intracellularly. The enzymatic digestion significantly altered the detectability of epitopes, resulting in an increase in continuous wall labelling within the intine across multiple probes. These findings indicate that enzymatic modification of pectic and mannan components has a considerable impact on the apparent distribution of hemicellulose epitopes within the pollen wall of G. lutea. Together, these results expand the still limited in situ immunolocalisation evidence base for hemicellulose-related epitopes in pollen, and provide a practical framework for interpreting digestion-dependent changes primarily in terms of epitope accessibility within the intine matrix. Full article
(This article belongs to the Special Issue Pollination Biology: 2nd Edition)
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15 pages, 621 KB  
Article
Phenotypic and Molecular Characterization of Clinical Isolates of Vancomycin-Resistant Enterococcus faecium in the Health District of Bolzano (Italy) During 2021–2023
by Angela Maria Di Pierro, Richard Aschbacher, Maria Del Grosso, Monica Monaco and Elisabetta Pagani
Pathogens 2026, 15(2), 143; https://doi.org/10.3390/pathogens15020143 (registering DOI) - 28 Jan 2026
Abstract
Vancomycin-resistant Enterococcus faecium (VREfm) is an emerging pathogen responsible for healthcare-associated infections. For this reason, 44 VREfm isolates collected during 2021–2023 were characterized using phenotypic and genomic approaches. VREfm isolates were identified by MALDI-TOF and antimicrobial susceptibility tests were performed with Vitek 2, [...] Read more.
Vancomycin-resistant Enterococcus faecium (VREfm) is an emerging pathogen responsible for healthcare-associated infections. For this reason, 44 VREfm isolates collected during 2021–2023 were characterized using phenotypic and genomic approaches. VREfm isolates were identified by MALDI-TOF and antimicrobial susceptibility tests were performed with Vitek 2, Sensititre, or E-test. Sequence type (ST), antibiotic resistance genes, virulence factors and genetic relatedness were determined using Next Generation Sequencing. Forty-three isolates had a VanA phenotype and vanHAX genotype and one had a VanB phenotype and vanHBX genotype. Isolates showed high antibiotic resistance to various antibiotics, but generally remained susceptible to quinupristin/dalfopristin, tigecycline and eravacycline. Two isolates were resistant to linezolid, showing the chromosomal mutation G2576T in domain V of the 23S rRNA gene in one isolate, and the transferable linezolid resistance genes cfr(D) and optrA in the other. Thirty-eight isolates belonged to ST80, one to ST17 (ST80 and ST17 are included in CC17) and one to ST697. Genomic analysis of the ST80 isolates showed that nearly all of them belonged to a single cluster. To prevent further spread of VREfm in the nosocomial environment, in addition to the application of up-to-date infection control strategies and antibiotic stewardship programs, the implementation of genomic surveillance is recommended. Full article
(This article belongs to the Special Issue Advances in the Epidemiology of Human Infectious Diseases)
20 pages, 1381 KB  
Systematic Review
AI-Enhanced Skill Assessment in Higher Vocational Education: A Systematic Review and Meta-Analysis
by Xia Sun and Haoheng Tian
Informatics 2026, 13(2), 20; https://doi.org/10.3390/informatics13020020 (registering DOI) - 28 Jan 2026
Abstract
This study synthesizes empirical evidence on AI-supported skill assessment systems in higher vocational education through a systematic review and meta-analysis. Despite growing interest in generative AI within higher education, empirical research on AI-enabled assessment remains fragmented and methodologically uneven, particularly in vocational contexts. [...] Read more.
This study synthesizes empirical evidence on AI-supported skill assessment systems in higher vocational education through a systematic review and meta-analysis. Despite growing interest in generative AI within higher education, empirical research on AI-enabled assessment remains fragmented and methodologically uneven, particularly in vocational contexts. Following PRISMA 2020 guidelines, 27 peer-reviewed empirical studies published between 2010 and 2024 were identified from major international and Chinese databases and included in the analysis. Using a random-effects model, the meta-analysis indicates a moderate positive association between AI-supported assessment systems and skill-related learning outcomes (Hedges’ g = 0.72), alongside substantial heterogeneity across study designs, outcome measures, and implementation contexts. Subgroup analyses suggest variation across regional and institutional settings, which should be interpreted cautiously given small sample sizes and diverse methodological approaches. Based on the synthesized evidence, the study proposes a conceptual AI-supported skill assessment framework that distinguishes empirically grounded components from forward-looking extensions related to generative AI. Rather than offering prescriptive solutions, the framework provides an evidence-informed baseline to support future research, system design, and responsible integration of generative AI in higher education assessment. Overall, the findings highlight both the potential and the current empirical limitations of AI-enabled assessment, underscoring the need for more robust, theory-informed, and transparent studies as generative AI applications continue to evolve. Full article
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17 pages, 4617 KB  
Article
Integrated mRNA-miRNA Analysis Reveals the Regulatory Network Under Salt–Alkali Stress in Alfalfa (Medicago sativa L.)
by Mengya Liu, Yanran Xu, Lijun Zhao, Haojie Yu, Lijun Shi, Wenxuan Zhu, Bai Du, Xiao Li and Ruicai Long
Agriculture 2026, 16(3), 323; https://doi.org/10.3390/agriculture16030323 (registering DOI) - 28 Jan 2026
Abstract
Soil salinization and alkalinization critically constrain alfalfa (Medicago sativa L.) productivity, yet the regulatory mechanisms underlying its responses to salt–alkali stress are not fully understood. In this study, the alfalfa variety “Zhongmu No. 1” was used as experimental material. The seeds were [...] Read more.
Soil salinization and alkalinization critically constrain alfalfa (Medicago sativa L.) productivity, yet the regulatory mechanisms underlying its responses to salt–alkali stress are not fully understood. In this study, the alfalfa variety “Zhongmu No. 1” was used as experimental material. The seeds were subjected to salt stress (75 mM NaCl), alkali stress (15 mM NaHCO3), and combined salt–alkali stress (50 mM NaCl + 5 mM NaHCO3) in dishes, with ddH2O serving as the control (CK). After 7 days of germination, the seedlings were transferred to a hydroponic system containing Hoagland nutrient solution supplemented with the corresponding treatments. Following 32 days of stress exposure, leaf and root tissue samples were collected for morphological and physiological measurements, as well as mRNA and miRNA sequencing analyses. Physiological assays revealed significant growth inhibition and increased electrolyte leakage under stress conditions. Transcriptome profiling identified over 5000 common differentially expressed genes (DEGs) in both leaves and roots under stress conditions, mainly enriched in pathways related to “iron ion binding”, “flavonoid biosynthesis”, “MAPK signaling”, and “alpha-Linolenic acid metabolism”. MiRNA sequencing detected 453 miRNAs, including 188 novel candidates, with several differentially expressed miRNAs (DEMs) exhibiting tissue- and stress-specific patterns. Integrated analysis revealed 147, 81, and 140 negatively correlated miRNA–mRNA pairs across three treatment groups, highlighting key regulatory modules in hormone signaling and metabolic pathways. Notably, in the ethylene and abscisic acid signaling pathways, ERF (XLOC_006645) and PP2C (MsG0180000476.01) were found to be regulated by miR5255 and miR172c, respectively, suggesting a post-transcriptional layer of hormonal control. DEM target genes enrichment pathway analyses also identified stress-specific regulation of “Fatty acid degradation”, “Galactose metabolism”, and “Fructose and mannose metabolism”. qRT-PCR validation confirmed the expression trends of selected DEGs and DEMs. Collectively, these findings reveal the complexity of miRNA–mRNA regulatory networks in alfalfa’s response to salt–alkali stress and provide candidate regulators for breeding stress-resilient cultivars. Full article
(This article belongs to the Special Issue Forage Breeding and Cultivation—2nd Edition)
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17 pages, 277 KB  
Article
Making Outer Space Legal: The “Appearance” of Extraterrestrial Intelligence at the Dawn of the Space Age
by Gabriela Radulescu
Histories 2026, 6(1), 12; https://doi.org/10.3390/histories6010012 (registering DOI) - 28 Jan 2026
Abstract
This paper addresses the knowledge gap on the beginning of the history of contact with extraterrestrial intelligent beings in international astronautics. In the mid-1950s, the world’s space law practitioner, Andrew G. Haley, proposed the concept of Metalaw, the law governing interactions between all [...] Read more.
This paper addresses the knowledge gap on the beginning of the history of contact with extraterrestrial intelligent beings in international astronautics. In the mid-1950s, the world’s space law practitioner, Andrew G. Haley, proposed the concept of Metalaw, the law governing interactions between all beings in the Universe, as he represented the American Rocket Society in the International Astronautical Congress, the single largest gathering of space-faring nations. Haley, with experience in radio communications law dating back to the 1930s, played a pivotal role in pushing for the international allocation of radio frequencies in space. Haley was, too, an agile mediator with the Soviet Union and its bloc, acting across various organizations and forums. This article, in contextualizing Haley’s introduction of Metalaw, shows how the onset of the Space Age coincided with the emergence of a contact scenario involving extraterrestrial intelligence enabled by the corresponding techno-scientific capabilities of the time. It demonstrates how extraterrestrial intelligence discursively addressed outer space regulation as a bone of contention between the two geopolitically divided parts, a regulation upon which the US’s global satellite system would depend. The analysis in this article recounts the birth of the Metalaw concept at the intersection of outer space imaginary, law, international organizations, science and technology, diplomacy, the Space Race, the Cold War, and radio astronomy’s Search for Extraterrestrial Intelligence. Full article
(This article belongs to the Section Political, Institutional, and Economy History)
24 pages, 7422 KB  
Article
Cytotoxic Effect of a β1,4-Galactosyltransferase Inhibitor in Hepatic Carcinoma Cells
by Zhe Dai, Ming Sun, Lihang Chen, Xueqi Fu, Wenfu Yan, Yin Gao and Inka Brockhausen
Cells 2026, 15(3), 251; https://doi.org/10.3390/cells15030251 (registering DOI) - 28 Jan 2026
Abstract
The incidence and mortality of hepatocellular carcinoma (HCC) are increasing worldwide, underscoring the need for novel therapeutic strategies. Synthetic 2-naphthyl 2-butanamido-2-deoxy-1-thio-β-d-glucopyranoside (612) is a selective inhibitor of β1,4-galactosyltransferase 1 (β4GalT1). In this study, we investigated the cytotoxic effects of [...] Read more.
The incidence and mortality of hepatocellular carcinoma (HCC) are increasing worldwide, underscoring the need for novel therapeutic strategies. Synthetic 2-naphthyl 2-butanamido-2-deoxy-1-thio-β-d-glucopyranoside (612) is a selective inhibitor of β1,4-galactosyltransferase 1 (β4GalT1). In this study, we investigated the cytotoxic effects of 612 across multiple cancer cell lines, with a focus on HCC, and explored the underlying mechanisms. We demonstrate that 612 preferentially exhibits cytotoxicity toward cancer cells with elevated expression of β4GalT family members, while human umbilical vein endothelial cells and immortalized human embryonic kidney epithelial cells are comparatively less sensitive. Treatment with 612 suppresses cancer cell migration and invasion and induces pronounced endoplasmic reticulum and Golgi stress, accompanied by G2/M cell cycle arrest. Furthermore, 612 activates apoptosis through ER stress–associated pathways by downregulating the anti-apoptotic protein Bcl-2 and upregulating pro-apoptotic proteins Bax and Bak, along with activation of caspase-3, -8, and -9. Collectively, these findings identify 612 as a promising anti-cancer candidate targeting β4GalTs-overexpressing HCC cells and warrant further therapeutic development. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins in Human Disease)
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11 pages, 250 KB  
Proceeding Paper
Landraces of Barley Exhibit Superior Drought Resistance: Insights from Agro-Morphological and Physiological Analysis
by Abhisek Shrestha, Bharti Thapa, Santosh Marahatta, Krishna Hari Dhakal, Dhurva Prasad Gauchan and Tirth Narayan Yadav
Biol. Life Sci. Forum 2025, 54(1), 11; https://doi.org/10.3390/blsf2025054011 (registering DOI) - 28 Jan 2026
Abstract
Barley is a marginalized crop subjected to several types of abiotic stress but need to intensify for future climate smart crop. This study investigated the drought resistance of barley landraces focusing on agro-morphological and physiological traits under controlled drought conditions. The experiment employed [...] Read more.
Barley is a marginalized crop subjected to several types of abiotic stress but need to intensify for future climate smart crop. This study investigated the drought resistance of barley landraces focusing on agro-morphological and physiological traits under controlled drought conditions. The experiment employed a two-factorial completely randomized design (CRD) with 14 barley landraces (of which 8 completed the maturity period examination) subjected to drought stress at three growth stages (CRI, tillering, and grain filling). Key parameters such as SPAD values (chlorophyll content), tiller number, and yield attributes were measured and analyzed using drought tolerance indices. Fourteen genotypes were initially tested, of which six failed to reach maturity; eight genotypes completed the full growth cycle and were used for yield and stress index analysis. Results revealed significant genotypic variation in drought response. Eight landraces exhibited higher SPAD values under drought, indicating better photosynthetic retention. Notably, AFU202501 demonstrated high yield stability (Stress Tolerance Index, STI = 1.782) under both stress and non-stress conditions, while Saptari Local showed exceptional drought avoidance (low Stress Susceptibility Index, SSI = −0.068) through early maturity and minimal yield reduction. In contrast, genotypes like Muktinath and NGRC 6010 were highly sensitive to drought, with significant yield losses (49–87%). Physiological traits such as chlorophyll retention and phenological plasticity (e.g., accelerated maturity under stress) were critical for drought adaptation. The findings highlight the potential of landraces like AFU202501 and Saptari Local as genetic resources for breeding climate-resilient barley varieties. The study underscores the importance of integrating traditional landraces into modern breeding programs to enhance food security in drought-prone regions. Full article
(This article belongs to the Proceedings of The 3rd International Online Conference on Agriculture)
24 pages, 693 KB  
Review
Natural Bioactive Compounds Targeting FABP4 in Adipogenesis and Obesity: Evidence from In Vitro and In Vivo Studies
by Jan Sobczyński, Filip Nowaczyński, Katarzyna Smolińska, Joanna Lachowicz-Radulska, Anna Serefko and Aleksandra Szopa
Int. J. Mol. Sci. 2026, 27(3), 1306; https://doi.org/10.3390/ijms27031306 (registering DOI) - 28 Jan 2026
Abstract
FABP4 (fatty acid-binding protein 4) is a lipid chaperone and secreted adipokine linking dysregulated fatty acid handling with inflammation, cellular stress, and insulin resistance in obesity. By modulating nuclear receptor signaling (notably PPARγ) and enhancing NF-κB/MAPK activation in adipocytes and macrophages, FABP4 contributes [...] Read more.
FABP4 (fatty acid-binding protein 4) is a lipid chaperone and secreted adipokine linking dysregulated fatty acid handling with inflammation, cellular stress, and insulin resistance in obesity. By modulating nuclear receptor signaling (notably PPARγ) and enhancing NF-κB/MAPK activation in adipocytes and macrophages, FABP4 contributes to maladaptive adipose remodeling and systemic metabolic decline. This review critically summarizes recent preclinical evidence on natural bioactive compounds that regulate FABP4 expression and associated adipogenic programs in models of adipogenesis and diet-induced obesity. Data from 3T3-L1/OP9 adipocytes, rodent studies, and selected alternative models indicate that many plant-derived extracts and phytochemicals (e.g., polyphenols, saponins, coumarins, terpenoids, and fermented products) down-regulate FABP4 at mRNA and/or protein levels. These effects are frequently accompanied by suppression of PPARγ/C/EBPα/SREBP1c signaling, activation of AMPK-related pathways, reduced lipid accumulation, and improved metabolic outcomes including lower weight gain, reduced adipocyte hypertrophy, improved steatosis, and favorable serum lipid profiles. Natural compounds from non-plant sources (animal- and microbe-derived metabolites) further broaden FABP4-targeting strategies, supporting FABP4 as a cross-class therapeutic node. Key translational barriers include poor extract standardization, incomplete identification of active constituents, limited oral bioavailability, microbiome-dependent variability, and scarce clinical validation. Future work should prioritize well-characterized lead scaffolds, targeted delivery, rational combinations, and standardized, adequately powered clinical trials assessing dose, durability of FABP4 suppression, and cardiometabolic safety. Full article
(This article belongs to the Special Issue Natural Compounds in Human Health and Disease)
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11 pages, 1126 KB  
Article
Raman Scattering Enhanced by Surface Plasmon Polaritons on Ag and Al Gratings
by Ivan Z. Indutnyi, Viktor I. Mynko, Volodymyr M. Dzhagan, Andrii A. Korchovyi, Nazar V. Mazur, Oleksandr M. Hreshchuk, Stanislav S. Serhiichuk, Volodymyr S. Yefanov and Volodymyr O. Yukhymchuk
Photonics 2026, 13(2), 120; https://doi.org/10.3390/photonics13020120 (registering DOI) - 28 Jan 2026
Abstract
This paper describes the development and characterization of surface-enhanced Raman spectroscopy (SERS) substrates that employ the excitation of surface plasmon polaritons (SPPs) on periodic metal diffraction gratings to amplify the Raman signal of an analyte. The gratings were fabricated via interference photolithography on [...] Read more.
This paper describes the development and characterization of surface-enhanced Raman spectroscopy (SERS) substrates that employ the excitation of surface plasmon polaritons (SPPs) on periodic metal diffraction gratings to amplify the Raman signal of an analyte. The gratings were fabricated via interference photolithography on As40S40Se20 thin films. The resulting surface relief was subsequently coated with either aluminium (Al gratings) or aluminium followed by silver (Ag gratings). The ratio of the relief depth to the grating period (h/a) was optimized to maximize SPP excitation efficiency. For both types of gratings, a strong angular dependence of the Raman scattering intensity of the analyte molecule (Rhodamine 6G) was observed, which anticorrelates with the angular dependence of the specularly reflected light intensity. The enhancement factor is 2 × 102 for the aluminium grating and 1 × 103 for the silver grating. This finding suggests that aluminium-based SERS substrates may serve as a cost-effective alternative to those coated with noble metals. Although the overall amplification is significantly lower than that achieved by SERS substrates based on localized surface plasmon (LSP) excitation, the grating-based SPP substrates offer a crucial advantage for quantitative measurements due to their uniform enhancement across the entire substrate area. Full article
(This article belongs to the Special Issue Advances in Raman Spectroscopy)
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20 pages, 1538 KB  
Systematic Review
The Pilates Method as a Therapeutic Intervention in Patients with Fibromyalgia: A Systematic Review and Meta-Analysis
by Gustavo Rodríguez-Fuentes, Alejandro Bermúdez-Rodas, Hugo Rodríguez-Otero and Pablo Campo-Prieto
Appl. Sci. 2026, 16(3), 1324; https://doi.org/10.3390/app16031324 (registering DOI) - 28 Jan 2026
Abstract
Fibromyalgia is a chronic condition characterized by widespread pain, fatigue, and reduced quality of life. Exercise therapy, including Pilates, is commonly recommended; however, current reviews report inconsistent findings across specific modalities. This PRISMA 2020 systematic review and meta-analysis with a PROSPERO-registered protocol, designed [...] Read more.
Fibromyalgia is a chronic condition characterized by widespread pain, fatigue, and reduced quality of life. Exercise therapy, including Pilates, is commonly recommended; however, current reviews report inconsistent findings across specific modalities. This PRISMA 2020 systematic review and meta-analysis with a PROSPERO-registered protocol, designed as a focused update of post-2020 RCTs complementing prior comprehensive syntheses, evaluated Pilates-based interventions for pain and fibromyalgia impact (FIQ). HRQoL outcomes were synthesized narratively due to heterogeneity in measurement instruments, and all outcomes were extracted at the first post-intervention assessment (no pooled long-term data were available). Seven RCTs (6–12 weeks; 2–3 sessions/week) met eligibility criteria. Methodological quality was generally moderate (PEDro), and risk of bias was assessed using RoB 2. Certainty of evidence (GRADE) was rated very low for pain and low for FIQ. Among trials reporting adherence (4/7), values ranged from 68% to 92%; adverse event monitoring was inconsistent (systematically reported in 2/7), limiting tolerability conclusions. Between-group effects versus active comparators were small and non-significant for pain (pooled Hedges’ g = −0.10, 95% CI [−0.83, 0.63], p = 0.79; I2 = 73%); this wide interval, spanning potential benefit to harm, precludes definitive conclusions. For FIQ, the primary (unadjusted) analysis was non-significant: pooled MD = −5.53 (95% CI [−11.96, 0.89], p = 0.09); sensitivity analysis using ANCOVA-adjusted estimates yielded MD = −6.71 (95% CI [−13.11, −0.30], p = 0.04). Both estimates remained below MCID thresholds and were sensitive to estimator choice. Absence of statistical significance does not demonstrate equivalence; non-inferiority designs with predefined margins would be required. Given very low (pain) to low (FIQ) certainty of evidence, adequately powered trials with standardized protocols and longer follow-up are needed to resolve uncertainty regarding Pilates’ comparative effectiveness within multimodal fibromyalgia management. Full article
(This article belongs to the Special Issue Advances in Neurological Physical Therapy)
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20 pages, 3648 KB  
Article
Histamine H1 Receptor-Mediated CREB Phosphorylation via Gq Protein Signaling and Arrestin Modulation
by Ryosuke Ogami, Shotaro Michinaga, Yosuke Iiboshi, Yasuhiro Ogawa and Shigeru Hishinuma
Pharmaceuticals 2026, 19(2), 227; https://doi.org/10.3390/ph19020227 (registering DOI) - 28 Jan 2026
Abstract
Background/Objectives: Histamine H1 receptors mediate multiple physiological and pathophysiological processes, including inflammation and allergy, by regulating downstream gene expression via transcription factors. cAMP response element-binding protein (CREB) is a major transcription factor whose phosphorylation is regulated by multiple signaling pathways. Although [...] Read more.
Background/Objectives: Histamine H1 receptors mediate multiple physiological and pathophysiological processes, including inflammation and allergy, by regulating downstream gene expression via transcription factors. cAMP response element-binding protein (CREB) is a major transcription factor whose phosphorylation is regulated by multiple signaling pathways. Although CREB is closely involved in multiple physiological and pathophysiological processes, the detailed intracellular signaling pathway of H1 receptor-mediated CREB phosphorylation remains to be elucidated. We investigated the roles of Gq proteins and arrestins in H1 receptor-mediated CREB phosphorylation. Methods: We constructed Chinese hamster ovary (CHO) expressing human wild-type (WT) H1 receptors and two types of C-terminal mutants. One mutant was constructed by truncating the serine 487 residue only at the C-terminus (S487Trunc), and the other was constructed by substituting the serine 487 residue at the C-terminus with alanine (S487A). S487Trunc is a Gq protein-biased while S487A is an arrestin-biased receptor. The expressions of CREB and its phosphorylated form were assessed by immunoblotting. Results: Histamine promoted CREB phosphorylation in CHO cells expressing WT or S487Trunc receptors, but not in cells expressing S487A. Inhibitors of protein kinase C (PKC), extracellular signal-regulated kinase (ERK), or c-Jun N-terminal kinase (JNK), and Ca2+ chelator suppressed histamine-induced CREB phosphorylation in CHO cells expressing WT or S487Trunc receptors. Basal CREB phosphorylation levels increased following β-arrestin overexpression and decreased after their siRNA-mediated knockdown, thus modulating histamine-stimulated CREB phosphorylation in WT CHO cells. Conclusions: H1 receptor-mediated CREB phosphorylation is induced through Gq protein/Ca2+/PKC-dependent ERK and JNK activation; arrestins can modulate this process by regulating basal CREB phosphorylation. Full article
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24 pages, 350 KB  
Article
Home Language Activities and Language Ability Between Chinese Preschool Children with Cochlear Implants and Children with Normal Hearing
by Meilin He and Inho Chung
Audiol. Res. 2026, 16(1), 18; https://doi.org/10.3390/audiolres16010018 (registering DOI) - 28 Jan 2026
Abstract
This study explored the relationship between different home language activities and language ability in Chinese preschoolers with cochlear implants (CIs) (mean age = 4.50, range = 3–5), comparing them with normally hearing (NH) peers (mean age = 4.66, range = 3–5). Correlation and [...] Read more.
This study explored the relationship between different home language activities and language ability in Chinese preschoolers with cochlear implants (CIs) (mean age = 4.50, range = 3–5), comparing them with normally hearing (NH) peers (mean age = 4.66, range = 3–5). Correlation and regression analyses revealed distinct predictive patterns between the two groups. In the CI group, although family literacy activities such as shared reading were associated with language skills, daily communication activities (e.g., conversational interactions) had a more significant predictive effect on language outcomes, even after controlling for key demographic variables. Conversely, for NH preschool children, family literacy activities showed a clearer independent association with language development. This study offers clearer insights for home-based rehabilitation practices among CI preschool children, suggesting that interventions should prioritize high-quality daily communication (e.g., open-ended questioning, extended dialog, contextualized interactions) rather than over-reliance on structured literacy activities. It also indicates that intervention models designed for NH preschool children cannot be simply applied. Full article
(This article belongs to the Section Speech and Language)
40 pages, 2475 KB  
Review
Research Progress of Deep Learning in Sea Ice Prediction
by Junlin Ran, Weimin Zhang and Yi Yu
Remote Sens. 2026, 18(3), 419; https://doi.org/10.3390/rs18030419 (registering DOI) - 28 Jan 2026
Abstract
Polar sea ice is undergoing rapid change, with recent record-low extents in both hemispheres, raising the demand for skillful predictions from days to seasons for navigation, ecosystem management, and climate risk assessment. Accurate sea ice prediction is essential for understanding coupled climate processes, [...] Read more.
Polar sea ice is undergoing rapid change, with recent record-low extents in both hemispheres, raising the demand for skillful predictions from days to seasons for navigation, ecosystem management, and climate risk assessment. Accurate sea ice prediction is essential for understanding coupled climate processes, supporting safe polar operations, and informing adaptation strategies. Physics-based numerical models remain the backbone of operational forecasting, but their skill is limited by uncertainties in coupled ocean–ice–atmosphere processes, parameterizations, and sparse observations, especially in the marginal ice zone and during melt seasons. Statistical and empirical models can provide useful baselines for low-dimensional indices or short lead times, yet they often struggle to represent high-dimensional, nonlinear interactions and regime shifts. This review synthesizes recent progress of DL for key sea ice prediction targets, including sea ice concentration/extent, thickness, and motion, and organizes methods into (i) sequential architectures (e.g., LSTM/GRU and temporal Transformers) for temporal dependencies, (ii) image-to-image and vision models (e.g., CNN/U-Net, vision Transformers, and diffusion or GAN-based generators) for spatial structures and downscaling, and (iii) spatiotemporal fusion frameworks that jointly model space–time dynamics. We further summarize hybrid strategies that integrate DL with numerical models through post-processing, emulation, and data assimilation, as well as physics-informed learning that embeds conservation laws or dynamical constraints. Despite rapid advances, challenges remain in generalization under non-stationary climate conditions, dataset shift, and physical consistency (e.g., mass/energy conservation), interpretability, and fair evaluation across regions and lead times. We conclude with practical recommendations for future research, including standardized benchmarks, uncertainty-aware probabilistic forecasting, physics-guided training and neural operators for long-range dynamics, and foundation models that leverage self-supervised pretraining on large-scale Earth observation archives. Full article
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