Life

19 pages, 2294 KB

Open AccessArticle

Neurocognitive Performance and Executive Functions Do Not Influence Conditioned Pain Modulation in Women with Migraine

by Juan C. Pacho-Hernández, Angela Tejera-Alonso, Ana I. de-la-Llave-Rincón, Silvia Ambite-Quesada, Cristina Gómez-Calero, Ricardo Ortega-Santiago, César Fernández-de-las-Peñas, Gustavo Plaza-Manzano, Juan A. Valera-Calero and Margarita Cigarán-Méndez

Life 2026, 16(1), 27; https://doi.org/10.3390/life16010027 - 24 Dec 2025

Abstract

Introduction: Migraine is featured by altered nociceptive processing and the presence of cognitive impairments. No study has previously investigated the influence of neurocognitive performance and executive functions in descending pain processing in this population. Aim: To assess the influence of neurocognitive [...] Read more.

Introduction: Migraine is featured by altered nociceptive processing and the presence of cognitive impairments. No study has previously investigated the influence of neurocognitive performance and executive functions in descending pain processing in this population. Aim: To assess the influence of neurocognitive processes and executive functions in conditioned pain modulation (CPM) activation in women with migraine. Methods: A cross-sectional case–control study including 140 women with migraine (50% chronic) and 70 control women was conducted. Clinical migraine features, neurocognitive processes (e.g., attention), and executive functions (memory, mental inhibition, speed of processing) were evaluated. Pressure pain thresholds (PPTs) were bilaterally assessed at the temporalis muscle, lateral epicondyle, and tibialis anterior muscle. Heat (HPT) and cold (CPT) pain thresholds were assessed at the frontalis (trigeminal area) muscle. Thus, CPM was evaluated with the cold pressor test paradigm by analyzing changes in mechanical/thermal stimuli after a conditioned stimulus. Results: Significant group*time interactions not associated with neurocognitive process/executive function, educational level, and employment status were found for PPTs at the temporalis muscle (Wilk’s λ = 0.588, F[2,199] = 69.756, p < 0.001, n²p = 0.412, 1 − β = 0.999), lateral epicondyle (Wilk’s λ = 0.674, F[2,200] = 48.331, p < 0.001, n²p = 0.326, 1 − β = 0.999), and tibialis anterior (Wilk’s λ = 0.751, F[2,200] = 33.110, p < 0.001, n²p= 0.249, 1 − β = 0.999): PPTs were higher after the conditioned stimulus in all points in control women (increases ranging from 11% to 17%), whereas PPTs were lower after the conditioned stimulus in women with migraine (decrease from −7.5% to −0.1%) when compared with PPTs at baseline. Changes in HPT and CPT were small and not significant, ranging from 0.1% to 0.5%. Conclusion: This study revealed that women with episodic or chronic migraine showed CPM deficits particularly against mechanical stimuli when compared with pain-free women. Neurocognitive (e.g., attention) processes or executive functions (e.g., working memory, mental inhibition) did not modulate CPM activity in women with migraine. Full article

(This article belongs to the Section Physiology and Pathology)

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13 pages, 896 KB

Open AccessArticle

Effect of Heat-Killed Lactiplantibacillus plantarum SNK12 on Sleep Quality and Stress-Related Neuroendocrine and Inflammatory Biomarkers in Adults: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial

by Takumi Watanabe, Shiho Kurosaka, Yuriko Namatame and Toshio Kawahara

Life 2026, 16(1), 26; https://doi.org/10.3390/life16010026 - 24 Dec 2025

Abstract

Heat-killed Lactiplantibacillus plantarum SNK12 (SNK), isolated from a traditional Japanese fermented food, has been suggested to influence sleep quality, but human data on sleep improvement with heat-killed lactic acid bacteria (postbiotics) remain limited. We conducted a randomized controlled trial to test whether heat-killed [...] Read more.

Heat-killed Lactiplantibacillus plantarum SNK12 (SNK), isolated from a traditional Japanese fermented food, has been suggested to influence sleep quality, but human data on sleep improvement with heat-killed lactic acid bacteria (postbiotics) remain limited. We conducted a randomized controlled trial to test whether heat-killed SNK (≥1 × 10¹¹ cells/day for 4 weeks) improves sleep quality and alters stress-related immune and neuroendocrine biomarkers. Healthy adults received SNK or a placebo for 4 weeks. The primary outcome was the Oguri–Shirakawa–Azumi Sleep Inventory MA version (OSA-MA) factor “Sleepiness on Rising”; secondary outcomes were other OSA-MA factors and the stress-related biomarkers salivary cortisol and plasma tumor necrosis factor-α (TNF-α). Compared with placebo, SNK improved Sleepiness on Rising (p = 0.032) and Initiation and Maintenance of Sleep (p = 0.010). Salivary cortisol (p = 0.016) and plasma TNF-α (p = 0.037) were also lower with SNK, and no safety concerns emerged. These concomitant changes in subjective sleep indices and stress-related biomarkers are consistent with modulation of hypothalamic–pituitary–adrenal axis activity and inflammatory pathways along the gut–brain axis. SNK may, therefore, represent a practical postbiotic option to support sleep quality. Full article

(This article belongs to the Section Medical Research)

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18 pages, 793 KB

Open AccessArticle

Effects of Sprint Interval Training on Brain Fatigue Resistance in Competitive Skateboarders: Evidence from EEG, HRV, and VAS Measures

by Mulin Yang, Yuqiang Guo and Kewei Zhao

Life 2026, 16(1), 25; https://doi.org/10.3390/life16010025 - 24 Dec 2025

Abstract

Purpose: This preliminary study examined the associations between a 6-week sprint interval training (SIT) program and mental-fatigue (MF) related neurophysiological and subjective indicators in elite skateboarders. Methods: In this preliminary study, a single-group, repeated-measures design was employed. Twelve elite skateboarders completed a 6-week [...] Read more.

Purpose: This preliminary study examined the associations between a 6-week sprint interval training (SIT) program and mental-fatigue (MF) related neurophysiological and subjective indicators in elite skateboarders. Methods: In this preliminary study, a single-group, repeated-measures design was employed. Twelve elite skateboarders completed a 6-week sprint interval training (SIT) program. Mental fatigue was assessed at three time points—pre-intervention (Week 0), mid-intervention (Week 3), and post-intervention (Week 6)—using a standardized 60 min Stroop task, with post-task EEG, HRV, and VAS measures collected to characterize neurophysiological and subjective responses. Results: Across the intervention, EEG indices indicated higher central nervous system activation and more stable post-task neural profiles. HRV indices suggested more flexible autonomic regulation, with favorable changes in low- and high-frequency components, sympathovagal balance, and recovery-related scores, whereas baseline-related indices such as RMSSD and SDNN showed no clear change. VAS ratings showed stable MF, accompanied by increased mental exertion and motivation and reduced physical fatigue over time. Conclusions: These preliminary findings suggest that a 6-week SIT program may be associated with enhanced resistance to Stroop-related MF in elite skateboarders, potentially through coordinated adaptations in neural activation, autonomic regulation, and psychological factors. Future randomized studies incorporating behavioral performance and sport-specific cognitive tasks are warranted to confirm and extend these observations. Full article

(This article belongs to the Topic Exercise and Human Aging: Physiological and Psychological Functions)

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23 pages, 2425 KB

Open AccessArticle

ADIPOQ Variants rs1501299 and rs3774261 and Hypoadiponectinemia in Obese Women with PCOS: Genetic and Metabolic Interactions

by Intissar Ezzidi, Sameh Sarray, Mahmoud A. Alfaqih and Nabil Mtiraoui

Life 2026, 16(1), 24; https://doi.org/10.3390/life16010024 - 23 Dec 2025

Abstract

Background: Hypoadiponectinemia, a metabolic hallmark of obesity, is common in polycystic ovary syndrome (PCOS) yet the association of variants in the ADIPOQ gene with obesity in PCOS remains uncertain. To investigate whether ADIPOQ variants are associated with obesity in PCOS in relation to [...] Read more.

Background: Hypoadiponectinemia, a metabolic hallmark of obesity, is common in polycystic ovary syndrome (PCOS) yet the association of variants in the ADIPOQ gene with obesity in PCOS remains uncertain. To investigate whether ADIPOQ variants are associated with obesity in PCOS in relation to circulating adiponectin levels, and whether integrating genotypes, adiponectin, and a polygenic risk score (PRS) improves risk stratification. Methodology: In 324 Tunisian women with PCOS, classified as obese or non-obese by WHO criteria, serum adiponectin was measured, and nine ADIPOQ variants were genotyped using TaqMan assays. Associations with obesity were assessed using logistic regression, gene phenotype interaction analysis, and models incorporating a PRS; epistasis, QTL, and diplotypes were also evaluated. Results: Adiponectin levels were significantly lower in obese women and modestly predicted obesity (AUC = 0.605). Variants rs1501299 and rs3774261 were significantly associated with obesity under recessive models (OR up to 5.18, 95% CI [2.32–11.56], p = 7.14 × 10⁻⁵). Risk genotypes and haplotypes correlated with reduced adiponectin and increased obesity risk, with adiponectin levels significantly associated with the genotype–obesity relationships. A combined model including adiponectin, the two variants, and PRS outperformed single predictors. Conclusions:ADIPOQ rs1501299 and rs3774261 are associated with obesity in women with PCOS, with this association demonstrating a specific relationship with reduced adiponectin. Integrating genetic and biochemical markers improves metabolic risk profiling and supports personalized management. Full article

(This article belongs to the Section Genetics and Genomics)

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12 pages, 1828 KB

Open AccessArticle

Retinal Carotenoid Supplementation Increases HDL Cholesterol in Humans and Mice

by Binxing Li, Emmanuel K. Addo, Fu-Yen Chang, Shukui Guo, Moses Awuni, Emily Conway, Jialai Ying, Dylan Ramos and Paul S. Bernstein

Life 2026, 16(1), 23; https://doi.org/10.3390/life16010023 - 23 Dec 2025

Abstract

Carotenoid supplementation may reduce the risk of age-related macular degeneration (AMD). These retinal nutrients are hydrophobic molecules obtained from the diet that are transported to the retina through high-density lipoprotein (HDL) complexes. HDL cholesterol is a recognized biomarker for AMD risk. This study [...] Read more.

Carotenoid supplementation may reduce the risk of age-related macular degeneration (AMD). These retinal nutrients are hydrophobic molecules obtained from the diet that are transported to the retina through high-density lipoprotein (HDL) complexes. HDL cholesterol is a recognized biomarker for AMD risk. This study examined the effect of carotenoid supplementation on circulating HDL cholesterol levels. Serum lipid profiles were measured in 20 participants from the Lutein and Zeaxanthin in Pregnancy (L-ZIP) trial, which enrolled 40 pregnant women. In addition to standard prenatal supplements, half received 10 mg of lutein and 2 mg of zeaxanthin daily from the first trimester, and half received a placebo. Carotenoid supplementation significantly increased HDL cholesterol in the third trimester, with no changes in total cholesterol, LDL cholesterol, or triglycerides (TG) across trimesters. To further evaluate individual carotenoids, serum lipids were analyzed in macular pigment transgenic mice fed lutein, zeaxanthin, or β-carotene for one month. All three carotenoids significantly increased HDL cholesterol and reduced TG levels, with the effect ranking as zeaxanthin > lutein > β-carotene. These findings suggest that carotenoid supplementation modulates the serum lipid profile—elevating HDL cholesterol and lowering TG—which may contribute to protection against AMD and other lipid-associated diseases. Full article

(This article belongs to the Section Physiology and Pathology)

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13 pages, 1777 KB

Open AccessArticle

White Matter N-Acylphosphatidylserines (NAPSs) and Myelin Dysfunction in Late-Onset Alzheimer’s Disease (LOAD): A Pilot Study

by Paul L. Wood, Annika K. Lagos and Alexis R. Kastigar

Life 2026, 16(1), 22; https://doi.org/10.3390/life16010022 - 23 Dec 2025

Abstract

Disruption of myelin in Alzheimer’s disease has been observed by various approaches including histology, proteomics, and white matter hyperintensities in T2 FLAIR images. Since lipids are essential myelin components, we aimed to monitor N-acylphosphatidylserines (NAPSs), unique brain lipids that are altered by neuronal [...] Read more.

Disruption of myelin in Alzheimer’s disease has been observed by various approaches including histology, proteomics, and white matter hyperintensities in T2 FLAIR images. Since lipids are essential myelin components, we aimed to monitor N-acylphosphatidylserines (NAPSs), unique brain lipids that are altered by neuronal stress. NAPS 52:1 (PS 36:1-N16:0) was the dominant NAPS in both gray and white matter. Relative levels of NAPS 52:1 were 2.5 times higher in the periventricular white matter (PVWM) than in the hippocampus and were reduced to approximately 50% of control in both brain regions in subjects with late-onset Alzheimer’s disease (LOAD). To monitor potential alterations in metabolic precursors of NAPS 52:1, we also measured the following: (1) phosphatidylcholine (PC) 36:1, which can undergo base exchange with N-acylserine (NASer) 16:0 to form NAPS 52:1; (2) phosphatidylserine (PS) 36:1, which can undergo N-acylation with palmitic acid (FA 16:0); and (3) diacylglycerol 36:1, which can be a precursor for both PC 36:1 and PS 36:1. These analyses found that only the relative levels of PS 36:1 were decreased and only in the PVWM. Next, we evaluated NASer 16:0, which can be released from NAPS 52:1 by phospholipase D. This is an N-acyl amino acid with neuroprotective properties. NASer 16:0 was found to be present at trace levels and could only be reliably monitored in the PVWM in which relative levels were decreased in LOAD subjects. In summary, reductions in NAPSs and NASer in the PVWM are lipid biomarkers of disruptions in myelin in LOAD. These data, in conjunction with our previous report of decrements in the levels of neocortical ether-PS in LOAD, suggest that these combined alterations in serine glycerophospholipid metabolism may contribute to neuronal dysfunction in dementia. Full article

(This article belongs to the Section Physiology and Pathology)

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17 pages, 10354 KB

Open AccessArticle

ISSR-Based Genetic Diversity and Structure of Medicago sativa L. Populations from the Aras Basin, a Crossroad of Gene Centers

by Baris Eren

Life 2026, 16(1), 21; https://doi.org/10.3390/life16010021 - 23 Dec 2025

Abstract

The Aras Basin, located at the intersection of three major gene centers, represents one of the most important transition zones for the evolution of forage legumes. This study evaluates the genetic diversity and population structure of 74 Medicago sativa genotypes, including wild populations [...] Read more.

The Aras Basin, located at the intersection of three major gene centers, represents one of the most important transition zones for the evolution of forage legumes. This study evaluates the genetic diversity and population structure of 74 Medicago sativa genotypes, including wild populations and commercial cultivars, using ISSR markers. The analysis revealed a broad level of genetic variability, reflecting the adaptive potential of alfalfa in this ecologically heterogeneous region. Population structure analyses consistently separated the germplasm into three genetic clusters, demonstrating clear differentiation between wild accessions and registered varieties. Geographical patterns were also evident, with genotypes from western, central, and eastern subregions forming distinct groups. These results highlight the unique genomic composition of alfalfa in the Aras Basin and demonstrate the value of ISSR markers for characterizing multilayered genetic variation in ecological transition zones. The findings provide a complementary genomic perspective that expands existing knowledge of M. sativa diversity and offers useful guidance for breeding programs and genetic resource conservation. Full article

(This article belongs to the Special Issue Evolutionary and Conservation Genetics: 3rd Edition)

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27 pages, 7997 KB

Open AccessArticle

Glyco-Architectural Remodelling of the Feline Heart: Age- and HCM-Related Insights from Lectin Histochemistry

by Irina Constantin, Romelia Pop, Andrada Negoescu, Dragoș Hodor, Mara Georgiana Haralambie, Raluca Marica and Flaviu-Alexandru Tăbăran

Life 2026, 16(1), 20; https://doi.org/10.3390/life16010020 - 22 Dec 2025

Abstract

Glycosylation plays a critical role in maintaining cardiac structure and function, yet its modulation during aging and hypertrophic cardiomyopathy (HCM) in feline hearts remains uncharacterized. This study provides a systematic analysis of lectin-binding patterns in feline myocardium across different age groups and disease [...] Read more.

Glycosylation plays a critical role in maintaining cardiac structure and function, yet its modulation during aging and hypertrophic cardiomyopathy (HCM) in feline hearts remains uncharacterized. This study provides a systematic analysis of lectin-binding patterns in feline myocardium across different age groups and disease states. Post-mortem feline hearts (n = 64), classified by age (newborn to senior) and diagnostic status (healthy vs. HCM-affected), were evaluated using tissue microarrays stained with five plant-derived lectins—Concanavalin A (ConA), Wheat Germ Agglutinin (WGA), RCA (Ricinus communis Agglutinin I), Tomato (Lycopersicon esculentum Agglutinin), and Griffonia (Bandeiraea) simplicifolia Lectin I (BS)—alongside Draq5 nuclear counterstaining. Lectin histochemistry revealed distinct, region-specific glycosylation patterns, with notable remodelling in both aged and HCM-affected hearts. These glycan alterations reflect underlying molecular and structural changes associated with cardiac aging and pathology. Although lectin histochemistry has been used to examine cardiac glycosylation in species such as mice, rats, zebrafish, and humans, comparable data for felines have been lacking, even if domestic cat represents a spontaneous model for human HCM. This study provides the first essential step in characterizing the feline cardiac glycosylation. The observed shifts in lectin-binding profiles reveal specific remodelling associated with aging and HCM in cats. These results provide a foundation for future studies assessing the utility of glycan motifs as potential post-mortem markers of disease progression in felines. Full article

(This article belongs to the Special Issue Veterinary Pathology and Veterinary Anatomy: 3rd Edition)

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16 pages, 548 KB

Open AccessArticle

Optimising Return to Work for Cardiovascular Patients: An Interdisciplinary Approach in Occupational Medicine and Cardiology

by Donatella Sansone, Antonella Cherubini, Fabiano Barbiero, Marina Bollini, Marcella Mauro, Andrea Di Lenarda, Francesca Rui, Luca Cegolon and Francesca Larese Filon

Life 2026, 16(1), 19; https://doi.org/10.3390/life16010019 - 22 Dec 2025

Abstract

Background: This study explored facilitators and barriers to return to work (RTW) after acute cardiovascular events or elective cardiac surgery, integrating clinical, functional, and occupational factors. Methods: A prospective cohort study was conducted at the Occupational Medicine and Cardiac Rehabilitation Units of the [...] Read more.

Background: This study explored facilitators and barriers to return to work (RTW) after acute cardiovascular events or elective cardiac surgery, integrating clinical, functional, and occupational factors. Methods: A prospective cohort study was conducted at the Occupational Medicine and Cardiac Rehabilitation Units of the Maggiore Hospital in Trieste, Italy. Employed adults (18–67 years) admitted for acute coronary syndrome, valve replacement, or thoracic aortic surgery between January 2024 and July 2025 were enrolled. Sociodemographic, clinical, and occupational data were collected alongside functional and psychosocial assessments, including the Work Ability Index (WAI) and EQ-5D-5L. Predictors of RTW were analyzed with Cox regression models. Results: Among 103 patients (mean age 56.8 years; 92.2% male), 77.7% returned to work after a mean of 58.9 days. Independent predictors of earlier RTW were self-employment (HR 5.08, 95% CI 2.52–10.27), occupational responsibility (HR 2.12, 95% CI 1.01–4.45), and percutaneous coronary intervention (HR 2.72, 95% CI 1.47–5.06). Higher job-related physical demands, arrhythmias, and cardiac rehabilitation participation were associated with delayed RTW. Mean WAI (37.2 ± 5.1) and EQ-5D index (0.92 ± 0.09; EQ-VAS 77.4 ± 12.9) indicated preserved function and quality of life. Conclusions: RTW after cardiovascular events is multifactorial. Integrating occupational medicine into cardiac rehabilitation is key to ensuring safe, sustainable reintegration. Full article

(This article belongs to the Special Issue Interdisciplinarity in Cardiovascular Diseases: From Pathophysiology to Diagnosis and Treatment—4th Edition)

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18 pages, 12006 KB

Open AccessArticle

Cells Co-Producing Insulin and Glucagon in Congenital Hyperinsulinism

by Yuliya Krivova, Alexandra Proshchina, Dmitry Otlyga, Diliara Gubaeva, Maria Melikyan and Sergey Saveliev

Life 2026, 16(1), 18; https://doi.org/10.3390/life16010018 - 22 Dec 2025

Abstract

Alterations of pancreatic islet cell phenotypes are well established in diabetic conditions and considered to be one of the possible causes of insulin deficiency. However, there is limited information about alterations of islet cell phenotypes in opposite metabolic conditions such as hypoglycemia in [...] Read more.

Alterations of pancreatic islet cell phenotypes are well established in diabetic conditions and considered to be one of the possible causes of insulin deficiency. However, there is limited information about alterations of islet cell phenotypes in opposite metabolic conditions such as hypoglycemia in infants with congenital hyperinsulinism (CHI). Surgical biopsies of the pancreas from six infants with diffuse CHI and five infants with focal CHI were examined using double immunofluorescence with antibodies against insulin, glucagon and the key transcriptional factor responsible for β-cell differentiation and maturation—PDX1. The phenotypes of cells within the pancreatic islets in diffuse CHI and within the focus in focal CHI were compared to those in unaltered pancreatic islets located outside the focus. In diffuse CHI, the proportion of bi-hormonal insulin+/glucagon+ cells was increased. Additionally, an increase in the proportion of insulin+ cells lacking PDX1 was observed in diffuse CHI and within the focus. It can be assumed that alterations of the phenotype of β-cells may occur under hypoglycemic conditions, but the role of islet cell plasticity in infants with CHI remains to be established. Full article

(This article belongs to the Section Physiology and Pathology)

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38 pages, 1245 KB

Open AccessReview

Rising Demand for Winter Crops Under Climate Change: Breeding for Winter Hardiness in Autumn-Sown Legumes

by Katalin Magyar-Tábori, Sripada M. Udupa, Alexandra Hanász, Csaba Juhász and Nóra Mendler-Drienyovszki

Life 2026, 16(1), 17; https://doi.org/10.3390/life16010017 - 22 Dec 2025

Abstract

Climate change in the Pannonian region is accelerating a shift toward autumn sowing of cool-season grain legumes (pea, faba bean, lentil, chickpea, lupine) to achieve higher yields, greater biomass production, enhanced nitrogen fixation, improved soil cover, and superior resource use efficiency compared with [...] Read more.

Climate change in the Pannonian region is accelerating a shift toward autumn sowing of cool-season grain legumes (pea, faba bean, lentil, chickpea, lupine) to achieve higher yields, greater biomass production, enhanced nitrogen fixation, improved soil cover, and superior resource use efficiency compared with spring sowing. However, successful overwintering depends on the availability of robust winter-hardy cultivars. This review synthesizes recent breeding advances, integrating traditional approaches—such as germplasm screening, hybridization, and field-based selection—with genomics-assisted strategies, including genome-wide association studies (GWAS), quantitative trait locus (QTL) mapping, marker-assisted selection (MAS), and CRISPR/Cas-mediated editing of CBF transcription factors. Key physiological mechanisms—LT₅₀ determination, cold acclimation, osmoprotectant accumulation (sugars, proline), and membrane stability—are assessed using field survival rates, electrolyte leakage assays, and chlorophyll fluorescence measurements. Despite challenges posed by genotype × environment interactions, variable winter severity, and polygenic trait control, the release of cultivars worldwide (e.g., ‘NS-Mraz’, ‘Lavinia F’, ‘Ghab series’, ‘Pinklevi’, and ‘Rézi’) and ongoing breeding programs demonstrate substantial progress. Future breeding efforts will increasingly rely on genomic selection (GS), high-throughput phenomics, pangenomics, and G×E modeling to accelerate the development of climate-resilient legume cultivars, ensuring stable and sustainable production under increasingly unpredictable winter conditions. Full article

(This article belongs to the Special Issue Effects of Environmental Factors on Challenges of Plant Breeding: 2nd Edition)

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17 pages, 1079 KB

Open AccessReview

Diabetes Mellitus and Atrial Fibrillation: Mechanistic Insights and Therapeutic Impacts of Glucose-Lowering Drugs

by Mihai Grigore, Andreea-Maria Grigore, Martin-Graur Ruxandra-Elena, Verde Ioana, Gabriela Uscoiu, Camelia Nicolae, Ana-Maria Balahura and Adriana-Mihaela Ilieșiu

Life 2026, 16(1), 16; https://doi.org/10.3390/life16010016 - 22 Dec 2025

Abstract

Background/Objectives: Diabetes mellitus (DM) represents a major global public health challenge and is consistently associated with an increased risk of atrial fibrillation (AF). Despite extensive epidemiological evidence linking the two conditions, the underlying mechanisms and the influence of glucose-lowering therapies on AF susceptibility [...] Read more.

Background/Objectives: Diabetes mellitus (DM) represents a major global public health challenge and is consistently associated with an increased risk of atrial fibrillation (AF). Despite extensive epidemiological evidence linking the two conditions, the underlying mechanisms and the influence of glucose-lowering therapies on AF susceptibility remain incompletely defined. This review aims to summarize the current knowledge on the pathophysiological pathways linking DM and AF and to assess the impact of commonly used antidiabetic therapies on arrhythmic risk. We conducted a narrative review of epidemiological studies, mechanistic research, and cardiovascular outcome trials that evaluate the association between DM and AF. We included data addressing structural, electrical, autonomic, metabolic, and inflammatory mechanisms of AF in diabetes, as well as clinical evidence regarding the impact of metformin, insulin, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium–glucose cotransporter-2 (SGLT-2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists on AF incidence or recurrence. Results: DM promotes AF development through multiple complementary mechanisms, including atrial fibrosis, electrical conduction abnormalities, autonomic dysfunction, inflammation, glycemic fluctuations, oxidative stress, and expansion of epicardial adipose tissue. These changes create a vulnerable atrial substrate that facilitates both initiation and maintenance of AF. Evidence from recent trials indicates that the arrhythmic effects of glucose-lowering therapies are heterogeneous. Metformin and SGLT-2 inhibitors appear to offer favorable or neutral effects on AF risk. GLP-1 receptor agonists provide substantial cardiovascular benefits, although their specific impact on AF remains under investigation. Insulin therapy has been linked to a higher AF risk, whereas DPP-4 inhibitors show an overall neutral effect with inconsistent findings across studies. Conclusions: AF in patients with DM results from complex interactions between metabolic disturbances, structural remodeling, and inflammatory activation. Although several antidiabetic drugs appear to have potential antiarrhythmic effects, further dedicated research is needed to clarify their role in AF prevention and management. Full article

(This article belongs to the Section Pharmaceutical Science)

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15 pages, 1846 KB

Open AccessArticle

Positive Selection in Aggression-Linked Genes and Their Protein Interaction Networks

by Asma Awadi, Zelalem Gebremariam Tolesa and Hichem Ben Slimen

Life 2026, 16(1), 15; https://doi.org/10.3390/life16010015 - 22 Dec 2025

Abstract

Aggressive behavior is a complex and multifactorial trait influenced by several genes and shaped by societal and cultural constraints. To trace adaptation signals and identify potential new genes related to aggressive behavior, we explored variations in nine genes previously linked to aggressive behavior, [...] Read more.

Aggressive behavior is a complex and multifactorial trait influenced by several genes and shaped by societal and cultural constraints. To trace adaptation signals and identify potential new genes related to aggressive behavior, we explored variations in nine genes previously linked to aggressive behavior, as well as their 74 interacting genes retrieved from the STRING database. We identified 15 SNPs under positive selection in four genes (SEC24B, NCOA2, CTNNA1, and ALDH3A2), with selection consistently confirmed by both iHS and xp-EHH analyses. Among these, 15 SNPs showed high pairwise F_ST values and pronounced allele frequency differences between populations, suggesting their potential role in the local adaptation of the studied populations. The functional importance of these SNPs was confirmed by ten acting as eQTLs and five located in transcription factor binding sequences. The observed selection signatures may reflect adaptation in diverse biological processes, including protein trafficking and signal transduction, cell proliferation and differentiation, endocrine regulation, and lipid and aldehyde detoxification. Although these processes are not directly linked to aggression, they may have downstream effects on neurodevelopmental and hormonal regulation that could indirectly influence behavioral phenotypes. Experimental validation is required to confirm these signals and to clarify their functional and biological significance. Full article

(This article belongs to the Section Evolutionary Biology)

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12 pages, 3027 KB

Open AccessCase Report

New Insights into Molecular Mechanisms and Radiomics in Non-Contrast CT for Aortic Dissection: A Case Report and Literature Review

by Jian-Cheng Tian, Jia-Hao Zhou, Jui-Yuan Chung, Po-Chen Lin, Giou-Teng Yiang, Ya-Chih Yang and Meng-Yu Wu

Life 2026, 16(1), 14; https://doi.org/10.3390/life16010014 - 22 Dec 2025

Abstract

Background: Computed tomography (CT) angiography is widely regarded as the gold standard for diagnosing acute aortic dissection. However, in patients with contraindications to iodinated contrast media, such as those with renal insufficiency or hemodynamic instability, non-contrast CT may offer a viable alternative for [...] Read more.

Background: Computed tomography (CT) angiography is widely regarded as the gold standard for diagnosing acute aortic dissection. However, in patients with contraindications to iodinated contrast media, such as those with renal insufficiency or hemodynamic instability, non-contrast CT may offer a viable alternative for initial evaluation. Understanding the molecular mechanisms underlying aortic dissection, including extracellular matrix degradation, smooth muscle cell apoptosis, and inflammatory pathways, is crucial for developing novel diagnostic and therapeutic approaches. This report describes a single case of acute Stanford type A aortic dissection initially detected on non-contrast CT. Case Presentation: We describe a 74-year-old man who presented to the emergency department with fever and suspected infection, but without chest pain. An incidental finding on non-contrast CT revealed ascending aortic dilatation, pericardial effusion, and a suspected intimal flap. Subsequent CT angiography confirmed a Stanford type A aortic dissection. Conclusions: This case highlights the potential value of non-contrast CT in the early detection of aortic dissection, particularly when CT angiography cannot be performed. Recent advances in artificial intelligence (AI) and radiomic analysis have shown promise in augmenting the diagnostic capabilities of non-contrast CT by identifying subtle imaging features that may correlate with underlying molecular pathology and elude human observers. Emerging evidence suggests that radiomic features may reflect molecular alterations in the aortic wall, including metalloproteinase activity, collagen degradation, and inflammatory cell infiltration. Incorporating AI-assisted interpretation alongside insights into molecular mechanisms could facilitate earlier diagnosis, improve risk stratification, and guide personalized treatment strategies in critically ill patients. Although non-contrast CT has limited sensitivity for aortic dissection, it may still reveal crucial findings in selected cases and should be considered when contrast-enhanced imaging is not feasible. Ongoing progress in AI, radiomics, and molecular biomarker research may further expand the clinical applications of non-contrast CT in emergency cardiovascular care and bridge the gap between imaging phenotypes and molecular endotypes. These findings are hypothesis-generating and require validation in larger cohorts before clinical generalization. Full article

(This article belongs to the Special Issue Current and Future Perspectives of Artificial Intelligence in Medicine)

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15 pages, 3093 KB

Open AccessReview

Acute Exercise-Induced Epinephrine Elevation Promotes Post-Learning Memory Consolidation: A Narrative Review of Mechanisms and Implementation Strategies

by Yiwan Zhang, Xuewan Lin, Gen Li and Songtao Wang

Life 2026, 16(1), 13; https://doi.org/10.3390/life16010013 - 22 Dec 2025

Abstract

Memory function is susceptible to decline with age, stress, and neurological diseases, highlighting the importance of exploring effective and sustainable strategies to enhance memory consolidation. Epinephrine plays a key role in memory consolidation; acute, moderate elevations enhance memory, while chronic high levels are [...] Read more.

Memory function is susceptible to decline with age, stress, and neurological diseases, highlighting the importance of exploring effective and sustainable strategies to enhance memory consolidation. Epinephrine plays a key role in memory consolidation; acute, moderate elevations enhance memory, while chronic high levels are inhibitory. Given the limitations of pharmacological interventions, this study aims to investigate exercise as a non-pharmacological means to promote post-learning memory consolidation by inducing acute epinephrine release, focusing on its mechanisms and optimized implementation strategies. This narrative review systematically reviews evidence from neurophysiology, molecular biology, and behavioral experiments and finds that exercise can safely and controllably activate the sympathetic–adrenal system, leading to a rapid rise in epinephrine. The release kinetics align highly with the critical time window for memory consolidation. Moderate-intensity aerobic exercise implemented within 30 min post-learning can significantly improve memory retention. The mechanisms involve not only epinephrine enhancing synaptic plasticity and LTP by activating hippocampal β-adrenergic receptors, but also synergistic effects across multiple systems, such as promoting osteocalcin signaling, upregulating BDNF expression, inducing neurogenesis, and optimizing cerebral metabolism and blood flow. Evidence suggests that exercise, as a non-pharmacological intervention, significantly enhances post-learning memory consolidation through the precise modulation of epinephrine release and multi-system synergy, offering both high efficacy and safety. Future research should focus on developing precise exercise prescriptions based on individual characteristics and leveraging wearable devices and digital technologies to improve intervention adherence and applicability, promoting its widespread use in educational and clinical settings. Full article

(This article belongs to the Section Physiology and Pathology)

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Graphical abstract

11 pages, 247 KB

Open AccessArticle

Factors Associated with Referral to Low Vision for Patients with Advanced Glaucoma

by Julia Ernst, Janice Huang, Jakob Tsosie and David J. Ramsey

Life 2026, 16(1), 12; https://doi.org/10.3390/life16010012 - 22 Dec 2025

Abstract

Glaucoma is one of the most common causes of irreversible visual impairment world wide. Providing low vision rehabilitation (LVR) services is a primary mode of support for patients with permanent vision loss. This retrospective, cross-sectional study evaluated the rate at which patients with [...] Read more.

Glaucoma is one of the most common causes of irreversible visual impairment world wide. Providing low vision rehabilitation (LVR) services is a primary mode of support for patients with permanent vision loss. This retrospective, cross-sectional study evaluated the rate at which patients with severe open-angle glaucoma (OAG) were referred for LVR services at an academic medical center. Patient demographics, glaucoma severity, appointment history, performance on visual field (VF) testing, presenting visual acuity (VA), and change in best-corrected visual acuity (BCVA) after low vision refraction were abstracted from the electronic record and summarized by using descriptive statistics. Logistic regression analysis was used to assess the relationship between study variables and the likelihood of referral for LVR evaluation. Out of 522 patients with severe OAG, 88% of whom qualified as having low vision, 14 were referred for an LVR evaluation (2.7%). Referrals were most strongly associated with VA (adjusted odds ratio [aOR], 7.20; 95% confidence interval [CI], 2.11–24.64, p = 0.001) but not glaucoma-associated VF loss (aOR, 0.90; 95% CI, 0.24–3.37, p = 0.876). Thirteen of 14 patients referred for LVR completed visits (93%). More than one-third of those patients improved in their better-seeing eye after a low vision refraction, gaining an average of −0.18 ± 0.24 logMAR (half gaining ≥2-lines of BCVA). Patients with severe OAG are at risk of progressive visual disability from their eye disease. We found, however, that the majority of these patients were not referred to LVR services, despite meeting eligibility criteria and growing evidence demonstrating their potential benefit. Full article

(This article belongs to the Section Medical Research)

11 pages, 482 KB

Open AccessArticle

Efficacy and Safety of Pirfenidone in Patients with Progressive Pulmonary Fibrosis: A Retrospective Single-Center Study

by Ju Hyun Oh, Jin Han Park, Ji Hoon Jang, Minyoung Her, Een Young Cho and Jae Ha Lee

Life 2026, 16(1), 11; https://doi.org/10.3390/life16010011 - 21 Dec 2025

Abstract

Progressive pulmonary fibrosis (PPF) is an emerging subset of fibrotic interstitial lung diseases (ILD), defined by progressive fibrosis despite standard treatment in patients with other than idiopathic pulmonary fibrosis. The international guidelines recommended the use of nintedanib for PPF, while evidence supporting pirfenidone [...] Read more.

Progressive pulmonary fibrosis (PPF) is an emerging subset of fibrotic interstitial lung diseases (ILD), defined by progressive fibrosis despite standard treatment in patients with other than idiopathic pulmonary fibrosis. The international guidelines recommended the use of nintedanib for PPF, while evidence supporting pirfenidone remains insufficient. In this study, we aimed to evaluate the efficacy and safety of pirfenidone in treating PPF. In this retrospective single-center study, we analyzed clinical data from patients with PPF who were treated with pirfenidone. Lung function data from six months before and after pirfenidone treatment were collected to assess changes over time. Missing values were imputed using a general linear mixed model (GLMM) for longitudinal data analysis. Of 33 subjects, the median age was 65.0 years, and 51.5% were female. Rheumatoid arthritis-related ILD was the most common subtype (45.5%). The median daily dose of pirfenidone was 600 mg, with a median treatment duration of 7.3 months. GLMM analysis showed a significant forced vital capacity (FVC) improvement, from −114 mL in the 6 months before treatment to +47.3 mL in the 6 months after treatment (p = 0.001). All adverse events related to pirfenidone were mild. In conclusion, the use of pirfenidone in PPF can potentially reduce the rate of FVC decline in real clinical practice. Full article

(This article belongs to the Special Issue Advances in Pulmonology: Transforming Diagnosis and Treatment of Lung Diseases)

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32 pages, 1326 KB

Open AccessReview

Cell Surface Markers of Mesenchymal Stem Cells: Current Knowledge and Advances in Characterization Technologies

by Angelo Santoro, Manuela Grimaldi, Carmen Marino, Enza Napolitano, Michela Buonocore and Anna Maria D’Ursi

Life 2026, 16(1), 10; https://doi.org/10.3390/life16010010 - 21 Dec 2025

Abstract

Mesenchymal stem cells (MSCs) are pivotal in regenerative medicine due to their high differentiation potential and therapeutic versatility. MSCs are multipotent cells capable of differentiating into adipocytes, chondroblasts, osteoblasts, and, under specific conditions, neural, myocyte, and epidermal lineages. This cell type contributes to [...] Read more.

Mesenchymal stem cells (MSCs) are pivotal in regenerative medicine due to their high differentiation potential and therapeutic versatility. MSCs are multipotent cells capable of differentiating into adipocytes, chondroblasts, osteoblasts, and, under specific conditions, neural, myocyte, and epidermal lineages. This cell type contributes to tissue repair, immunomodulation, and regenerative therapies for cardiac, orthopedic, and hematological disorders. Accurate identification and characterization of these stem cells are essential for both research and clinical applications. MSCs are typically defined by plastic adherence, expression of surface markers CD105, CD73, and CD90, low or absent expression of hematopoietic markers (CD45, CD34), and in vitro differentiation potential. Understanding the expression patterns and functional relevance of these surface markers is critical for improving isolation strategies, enhancing therapeutic efficacy, and minimizing adverse effects. This review provides a comprehensive overview of the principal surface markers of MSCs, highlighting their significance in stem cell biology and clinical translation. Full article

(This article belongs to the Special Issue Unlocking New Biochemical Pathways: A Bridge for Drug Development in Human and Animal Diseases)

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14 pages, 9960 KB

Open AccessArticle

Biomechanical Investigation of Head Injuries Caused by Baseball Bat Strikes with Different Bat Sizes and Velocities: A Finite Element Simulation Study

by Han Zhang, Jin Yang, Luyi Guo, Jiani Sun, Shangxiao Li and Weiya Hao

Life 2026, 16(1), 9; https://doi.org/10.3390/life16010009 (registering DOI) - 20 Dec 2025

Abstract

Objective: Traumatic brain injury (TBI) represents a significant clinical problem, with the biomechanical mechanisms of striking from different blunt instruments remaining unclear. This study aims to quantitatively evaluate TBI severity under blunt strikes and to assess the effects of strike velocity and blunt [...] Read more.

Objective: Traumatic brain injury (TBI) represents a significant clinical problem, with the biomechanical mechanisms of striking from different blunt instruments remaining unclear. This study aims to quantitatively evaluate TBI severity under blunt strikes and to assess the effects of strike velocity and blunt instrument size on biomechanical responses to provide a finite element approach for investigating injury mechanisms and informing clinical diagnosis. Methods: A head finite element model incorporating an outer cortical-cancellous-inner cortical bone structure was developed and verified against a previous cadaveric impact study. Strike velocities and blunt instrument parameters, obtained from experiments in which a long bat (LB) and a short bat (SB) were used to strike a dummy head, were applied as the loading conditions in the finite element simulation. Kinetic energy (KE), internal energy (IE), impact force, von Mises stress on skull, intracranial pressure (ICP), and Head_3ms acceleration were analyzed as indicators of injury severity. Results: Simulated force and ICP responses agreed with cadaveric experimental data within a 9.8% error. With increasing strike velocity (10–30 m/s), KE, IE, impact force, ICP, and Head_3ms all rose, while von Mises stress evolved from localized to dispersed distribution. Head_3ms reached an injury threshold of 80 g at a strike velocity of 10 m/s, and ICP peaks for LB and SB exceeded the brain injury threshold (235 kPa, ≈1760 mmHg) at 12 m/s and 14 m/s, respectively. At the same velocity, LB generated higher KE, IE, impact force, ICP and Head_3ms than SB. At 30 m/s, LB generated 390 J KE and 29.0 kN peak force, which were 50.0% and 11.1% higher than those of SB (260 J, 26.1 kN). Conclusion: This study reveals that increasing strike velocity and employing a larger blunt instrument elevate biomechanical responses, resulting in von Mises stress transitioning from localized concentration to multipolar dispersion. Specifically, when striking the head with the LB at velocities exceeding 12 m/s or with the SB exceeding 14 m/s, the impacts indicate a severely life-threatening level. These findings deepen our understanding of the mechanisms of blunt TBI. The constructed and validated finite element model can be repeatedly used for computer simulations of TBI under various blunt striking conditions, providing a scientific basis for clinical diagnosis and surgical planning. Full article

(This article belongs to the Special Issue Traumatic Brain Injury (TBI))

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