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19 pages, 2884 KB  
Article
Distribution of HLA-G Alleles and Oncogenic Viruses in Laryngeal Squamous Cell Carcinoma
by Ljiljana Božić, Aleksandra Šmitran, Maja Travar, Dalibor Vranješ, Aleksandar Martinović, Sanja Jovičić and Aleksandra Knežević
Microbiol. Res. 2026, 17(9), 173; https://doi.org/10.3390/microbiolres17090173 - 7 Sep 2026
Abstract
HLA-G polymorphisms and various oncogenic viruses have been demonstrated in cancers of different anatomical sites. The study aimed to investigate the distribution and potential association of HLA-G alleles and the presence of human papillomavirus (HPV), Epstein–Barr virus (EBV), BK polyomavirus (BKPyV), and JC [...] Read more.
HLA-G polymorphisms and various oncogenic viruses have been demonstrated in cancers of different anatomical sites. The study aimed to investigate the distribution and potential association of HLA-G alleles and the presence of human papillomavirus (HPV), Epstein–Barr virus (EBV), BK polyomavirus (BKPyV), and JC polyomavirus (JCPyV) in laryngeal squamous cell carcinoma (LSCC) tissues. A total of 30 frozen tissues were analyzed using nested PCR for HPV detection and EBV detection and genotyping, and semi-nested PCR for BKPyV and JCPyV. Genotyping of HLA-G and HPV was performed by direct sequencing. HLA-G*01:01:01 predominated among the six alleles detected (p < 0.001). HPV was detected in 12 patients, EBV in 11, BKPyV in two patients, and JCPyV in none. High-risk HPV genotypes (16, 18, 66) were significantly more common in comparison to the low-risk genotype (HPV 6) (p = 0.01). Both EBV genotypes were detected, with EBV-1 predominating. Single infection was detected in nine tissues while co-infection was identified in eight LSCC tissues. HPV/EBV co-infection was the most prevalent finding and this difference was statistically significant (p = 0.03). A correlation of HLA-G alleles and the presence of single or viral co-infection was not found. Further investigations with a larger experimental and control cohort are needed to assess their effect on LSCC development. Full article
(This article belongs to the Section Medical and Veterinary Microbiology)
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14 pages, 11127 KB  
Article
Epidemiological Characteristics and Evolutionary Characterization of Human Metapneumovirus in Jiaxing, China
by Yamei Zhou, Yanqian Wu, Peiyan He, Yong Yan, Ganglin Ren, Xiaofei Zhang, Yin Song and Guoyin Zhu
Viruses 2026, 18(9), 978; https://doi.org/10.3390/v18090978 - 4 Sep 2026
Viewed by 122
Abstract
Human metapneumovirus (hMPV) represents a leading cause of both upper and lower respiratory tract infections among children and adults globally. To investigate the prevalence and evolution of hMPV in the Jiaxing area of China between 2023 and 2025, we screened 3600 pharyngeal swab [...] Read more.
Human metapneumovirus (hMPV) represents a leading cause of both upper and lower respiratory tract infections among children and adults globally. To investigate the prevalence and evolution of hMPV in the Jiaxing area of China between 2023 and 2025, we screened 3600 pharyngeal swab specimens by real-time PCR, identified 101 positives, and obtained genomic sequences of 48 viral isolates using high-throughput sequencing. Using the sequencing data, we reconstructed a phylogenetic tree and examined amino acid substitutions. The epidemiological analysis revealed an overall hMPV positivity rate of 2.81% (101/3600) in Jiaxing during 2023–2025. Although positive cases were detected across all age groups, they were mainly children, with no significant difference between genders. Regarding seasonal patterns, the peak of hMPV activity occurred predominantly during winter and spring. Over the study period, four genotypes co-circulated, in the order of B2 (41.67%), A2.2.2 (37.50%), A2.2.1 (16.67%), and B1 (4.17%). Further phylogenetic analysis showed that the B1 strains from Jiaxing clustered primarily with those from Beijing, China, while B2, A2.2.1, and A2.2.2 strains were more closely related to strains from the United States and Beijing. Of note, an A2c111nt-dup variant was identified in Jiaxing in 2023. Starting from November 2024, the prevailing genotype transitioned from A2.2.1/A2.2.2 to B2, and B2 emerged as the absolutely dominant strain by 2025. In comparison with earlier circulating strains, several amino acid substitutions have accumulated in current isolates, such as T223N, D280N, I392T, R396Q, S444N, K450R, and T521A in the F protein of B2 strains. Furthermore, the G, L, P, and SH proteins also displayed temporally patterned amino acid replacements. While the biological significance of these mutations is yet to be determined, these results highlight the public health importance of ongoing hMPV surveillance and dynamic monitoring of its genetic evolution. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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18 pages, 1407 KB  
Article
Genetic Polymorphisms CYP3A4*22, CYP3A5*3, and CYP2D6 Predicted Phenotypes Are Not Associated with Antipsychotic Treatment Outcomes in Neurotypical Prepubertal Boys with Conduct Disorders
by Dmitriy V. Ivashchenko, Mikhail D. Che, Farid R. Aysin, Svetlana N. Tuchkova, Ivan N. Korsakov, Ekaterina I. Ianavichiute, Mariia A. Ivashchenko, Pavel V. Shimanov, Rimma V. Kondratieva, Artem V. Shubin, Karin B. Mirzaev, Yuriy S. Shevchenko and Dmitry A. Sychev
Pharmaceuticals 2026, 19(9), 1401; https://doi.org/10.3390/ph19091401 - 4 Sep 2026
Viewed by 81
Abstract
Objectives. To identify associations between CYP3A4*22 and CYP3A5*3 genotypes, CYP2D6 phenotype, and the effectiveness and safety of antipsychotics in neurotypically developed boys with conduct disorders. Methods: The study included neurotypically developed boys aged 7–12 years who were hospitalized for conduct disorders. All [...] Read more.
Objectives. To identify associations between CYP3A4*22 and CYP3A5*3 genotypes, CYP2D6 phenotype, and the effectiveness and safety of antipsychotics in neurotypically developed boys with conduct disorders. Methods: The study included neurotypically developed boys aged 7–12 years who were hospitalized for conduct disorders. All patients were prescribed an antipsychotic. Patient follow-up lasted 14 days. Treatment effectiveness was assessed using a clinical aggression assessment (checklist) and the CGI-S, CGI-I, and CGAS scales. Safety was assessed using the UKU SERS and SAS scales. Patients were examined upon enrollment in the study, on day 5, and on day 14. All patients were genotyped for the CYP3A4*22 (rs35599367, C>T), CYP3A5*3 (rs776746, 6986T>C) CYP2D6*3 (rs35742686), CYP2D6*4 (G1846A, rs3892097), CYP2D6*6 (rs5030655), CYP2D6*10 (C100T, rs1065852), CYP2D6*41 (rs28371725) loci. CYP2D6 metabolism type was determined based on genotyping results, and patients were divided into two subgroups: those with normal metabolism (NM) and those with intermediate or poor metabolism (IM + PM). Results: Patients taking carbamazepine (n = 11) were excluded from the analysis of associations between treatment outcomes and the CYP3A4*22 and CYP3A5*3 polymorphisms. The analysis of associations between treatment outcomes and CYP2D6 metabolism type was conducted in two stages: the overall sample and a subsample of patients who were prescribed risperidone (n = 80). No significant associations were found between carrier status of the CYP3A4*22 and CYP3A5*3 polymorphisms and treatment effectiveness parameters. Analysis of the overall sample did not reveal any significant associations between CYP2D6 metabolism subtypes and the effectiveness parameters of drug therapy. Analysis of patients receiving risperidone revealed one statistically significant association: patients with CYP2D6 IM + PM reported headaches more frequently (16.1% vs. 2%; p = 0.03). Carrier status of the CYP3A4*22 polymorphism was significantly associated with asthenia and lethargy on day 5 (50% vs. 9.4%; p = 0.008). Conclusions: Our study identified only a few significant associations between the CYP3A4*22 polymorphism, CYP2D6 slow metabolism, and patients’ reports of early adverse reactions in a 14-day observation period. Further research is needed to identify pharmacogenetic predictors of the efficacy and safety of antipsychotics in neurotypical children with conduct disorders. Full article
(This article belongs to the Section Pharmacology)
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23 pages, 2360 KB  
Article
Bioactive and Nutritional Profiling of Freeze-Dried Pigmented Sweet Potato Powders: Antioxidant Capacity, Phenolic Compounds, and Mineral Composition
by Nicoleta Cristina Chiorean, Maria Simona Chiș, Alexandru Ioan Apahidean, Rodica Sima, Anca Corina Fărcaș, Adriana Păucean, Anamaria Iulia Török, Oana Cadar, Gina Maria Cucuiet, Gheorghe Coteț and Emese Gal
Appl. Sci. 2026, 16(17), 8815; https://doi.org/10.3390/app16178815 - 4 Sep 2026
Viewed by 169
Abstract
Freeze-dried sweet potato powders derived from three distinct genotypes—white (Koretta), orange (Ro-Ch-G), and purple (Ro-Ch-M)—were comprehensively characterized with respect to their proximate composition, phenolic profile, antioxidant activity, color attributes, and mineral composition. The purple sweet potato powder showed the highest total phenolic content [...] Read more.
Freeze-dried sweet potato powders derived from three distinct genotypes—white (Koretta), orange (Ro-Ch-G), and purple (Ro-Ch-M)—were comprehensively characterized with respect to their proximate composition, phenolic profile, antioxidant activity, color attributes, and mineral composition. The purple sweet potato powder showed the highest total phenolic content (5.79 mg GAE/g dw), flavonoid content (0.38 mg QE/g dw), and DPPH, ABTS and FRAP radical-scavenging activity (DPPH: 8.8 μM TE/g dw; ABTS: 11.7 μM TE/g dw; FRAP: 13.32 μM TE/g dw). In contrast, the white sweet potato powder exhibited the lowest values. HPLC-DAD-MS analysis revealed 19 tentatively identified phenolic compounds, with anthocyanins detected exclusively in the purple sample, which might be associated with its higher antioxidant activity. Color measurements showed distinct profiles among the analyzed composite powders. The purple sweet potato powder exhibited the lowest lightness (L) and hue angle values, whereas the orange sweet potato powder showed the highest b and chroma values, consistent with its characteristic orange pigmentation. Mineral and elemental analysis also showed variation in macro-, micro-, and trace-element composition among the composite powders, with the pigmented samples generally exhibiting higher concentrations of several elements, including K, Ca, Mn, P, and Zn. The resulting freeze-dried powders exhibited a diverse profile of quantifiable bioactive compounds, particularly in the purple sweet potato powder, supporting their compositional interest for further investigation in food applications. Full article
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16 pages, 6929 KB  
Article
A G4P[13] Porcine Rotavirus a Strain with Genomic Features Suggestive of Reassortment: Isolation, Genomic Characterization, and Pathogenicity in Piglets
by Xianyu Zhang, Rui Geng, Shengjin Liu, Liguo Gao, Qunhui Li, Yongchang Cao, Yu Wu and Hanqin Shen
Vet. Sci. 2026, 13(9), 907; https://doi.org/10.3390/vetsci13090907 - 4 Sep 2026
Viewed by 118
Abstract
Porcine rotavirus A (PoRVA) is an important cause of diarrhea in neonatal piglets, resulting in significant economic losses in the swine industry. In this study, a PoRVA strain, designated QY, was isolated from diarrheic piglets and systematically characterized. The virus was propagated in [...] Read more.
Porcine rotavirus A (PoRVA) is an important cause of diarrhea in neonatal piglets, resulting in significant economic losses in the swine industry. In this study, a PoRVA strain, designated QY, was isolated from diarrheic piglets and systematically characterized. The virus was propagated in MA104 cells and identified by immunofluorescence assay and transmission electron microscopy, showing typical cytopathic effects and spherical particles of approximately 70 nm. Whole-genome sequencing and phylogenetic analysis revealed that QY was a G4P[13] strain with a genotype constellation of G4–P[13]–I1–C1–M1–R1–A8–N1–T1–E1–H1. Several genome segments showed close phylogenetic relationships with human- or bat-associated RVA strains, a pattern consistent with a possible reassortment history of QY. Experimental infection showed that QY caused watery diarrhea, intestinal lesions, and viral shedding in neonatal piglets under the experimental conditions used in this study. High viral loads were detected in small intestinal tissues, accompanied by villous atrophy and epithelial degeneration. These findings provide new insights into the genetic diversity and evolution of PoRVA and further characterize the pathogenicity of the G4P[13] QY strain in neonatal piglets. Full article
(This article belongs to the Special Issue Porcine Health Management: Virus Infection and Epidemic Disease)
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22 pages, 680 KB  
Review
The Rhizosphere Microbiome: A Key Mediator of Crop Responses to Fertilization Strategies
by Zhihui Zhao, Qihua Wu, Zerong Sun, Wenling Zhou and Junhua Ao
Plants 2026, 15(17), 2711; https://doi.org/10.3390/plants15172711 - 3 Sep 2026
Viewed by 135
Abstract
The rhizosphere microbiome, the plant’s “second genome” is pivotal for crop nutrient acquisition, health, and stress responses. While fertilization ensures high agricultural yields, a key challenge is reshaping this microbiome to boost crop performance. This review synthesizes how mineral, organic, and bio-organic/microbial inoculant [...] Read more.
The rhizosphere microbiome, the plant’s “second genome” is pivotal for crop nutrient acquisition, health, and stress responses. While fertilization ensures high agricultural yields, a key challenge is reshaping this microbiome to boost crop performance. This review synthesizes how mineral, organic, and bio-organic/microbial inoculant fertilizers affect rhizosphere microbial structure, diversity, and function. Long-term excessive mineral fertilizers (especially nitrogen) reduce microbial diversity, diminish beneficial groups (e.g., diazotrophs, PGPR), and disrupt microbial networks via soil acidification and altered root exudates, causing continuous cropping obstacles. In contrast, organic fertilizers improve soil microenvironments, maintaining high microbial diversity, enriching beneficial taxa (e.g., Proteobacteria, Actinobacteria), and enhancing community complexity. Bio-organic fertilizers/microbial inoculants “engineer” the microbiome by introducing exogenous beneficial microbes (e.g., Bacillus, Pseudomonas, AMF), directly promoting growth, suppressing diseases, and “reconditioning” indigenous beneficial communities. We also clarify how fertilization regulates plant-microbe dialog via root exudates and rhizosphere chemistry (e.g., pH, ion balance), discuss current challenges (causality, lab-to-field translation, genotype-microbiome-fertilization interactions), and outline future directions. Integrating rhizosphere microbiome management into fertilization is crucial for reducing chemical fertilizer reliance and advancing agricultural green transformation. Full article
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14 pages, 327 KB  
Article
Effect of Homo- and Heterofermentative Silage Additives on the Quality and In Vitro Rumen Digestibility of Two Different Triticale Cultivars
by Eren Kuter, Derya Merve Karagöz, Muhammad Shazaib Ramay, Anas Tahir, Syed Umer Akhter, Bekir Tosun, Ifrah Raza, Murat Er, Dilan Kuter and Umair Ahsan
Fermentation 2026, 12(9), 417; https://doi.org/10.3390/fermentation12090417 - 1 Sep 2026
Viewed by 150
Abstract
Triticale, a hybrid cereal crop derived from the cross of wheat and rye, is widely used for silage production owing to its high nutritional qualities and tolerance to varying climatic conditions. The genotype and maturity stage of forage crops govern the efficiency of [...] Read more.
Triticale, a hybrid cereal crop derived from the cross of wheat and rye, is widely used for silage production owing to its high nutritional qualities and tolerance to varying climatic conditions. The genotype and maturity stage of forage crops govern the efficiency of microbial inoculants used for ensiling. The effects of homofermentative (HMF; Lactiplantibacillus plantarum and Enterococcus faecium) and heterofermentative (HTF; Lentilactobacillus buchneri) inoculants, either alone or in combination, on the fermentation quality, nutrient composition, and in vitro rumen digestibility of ensiled triticale varieties (Alperbey and Karma 2000) were assessed in this study. The study was carried out using a 2 × 2 × 2 factorial arrangement of two triticale varieties, two levels of HMF [0 or 1 × 105 CFU/g fresh forage (0.8 mg/kg)], and two levels of HTF [0 or 0.5 × 105 CFU/g fresh forage (500 mg/kg)]. Forages were harvested at the early dough stage, vacuum-packed in 110 μm-thick plastic bags (35 cm × 25 cm), and allowed to ferment for 120 days. Fermentation characteristics, chemical composition, volatile fatty acids, and digestibility traits were evaluated after ensiling. Application of HMF inoculant significantly reduced silage pH compared to the control and HTF treatments in Alperbey, whereas in Karma 2000, terminal pH remained statistically similar between control and HMF treatments. Generally, inoculated silages had lower ammonia nitrogen levels than control silages, reflecting better protein conservation. The HTF significantly increased the acetic acid and decreased the butyric acid concentrations. There were significant two-way (variety × HMF and variety × HTF) and three-way (variety × HMF × HTF) interactions for crude protein content, fiber contents, volatile fatty acids profile, and digestibility characteristics (p < 0.05). For Karma 2000, the application of HMF increased crude protein concentration; however, it also increased lignin and fiber contents, thereby reducing organic matter digestibility. In contrast, dual inoculation raised neutral detergent fiber digestibility. The results show that variety-specific inoculant selection can improve triticale silage quality, underscoring the importance of aligning microbial additives with the forage’s biochemical properties. Full article
(This article belongs to the Special Issue Fermentation Technologies for Sustainable Animal Feed)
22 pages, 1611 KB  
Article
MIF Promoter Variant rs755622 (−173G/C) in Younger and Older Turkish Adults: An Exploratory Cross-Sectional Genetic and in Silico Analysis
by Kursat Ozdilli, Gozde Oztan, Yeliz Ogret, Rustu Oguz, Hayriye Senturk Ciftci, Filiz Aydın and Fatma Oguz
Int. J. Mol. Sci. 2026, 27(17), 7818; https://doi.org/10.3390/ijms27177818 - 31 Aug 2026
Viewed by 160
Abstract
Age-associated immune–inflammatory remodeling may be influenced by regulatory variation in the macrophage migration inhibitory factor gene (MIF). We conducted an exploratory cross-sectional comparison to assess whether MIF rs755622 (−173G/C) genotype distributions differ between predefined younger and older age groups in a [...] Read more.
Age-associated immune–inflammatory remodeling may be influenced by regulatory variation in the macrophage migration inhibitory factor gene (MIF). We conducted an exploratory cross-sectional comparison to assess whether MIF rs755622 (−173G/C) genotype distributions differ between predefined younger and older age groups in a Turkish population and to characterize the observed pattern using genetic-model and in silico analyses. We evaluated 368 individuals: 245 older adults aged 65–102 years and 123 younger controls aged 20–46 years. None of the 26 main association tests remained statistically significant after global multiplicity correction (minimum FDR q = 0.062; minimum Bonferroni-adjusted p = 0.108). Before correction, GC frequency was higher in the older group and increased across the ordered age categories, and sex-adjusted analyses yielded concordant nominal estimates. However, these nominal patterns were sensitive to younger-control genotype reclassification and were not supported by an allele-level or additive association. Younger controls showed Hardy–Weinberg disequilibrium (p < 0.001), without sequencing confirmation, and deterministic and scenario-based Monte Carlo genotype-reclassification analyses indicated sensitivity of the nominal signal to uncertainty in control genotype classification. GTEx data provide C-allele-oriented expression context but do not validate function in this cohort. These preliminary findings warrant independent genotype verification, ancestry-matched replication, and direct functional investigation in future studies. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Environment-Induced Human Diseases)
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32 pages, 6960 KB  
Article
Explainable TabPFN-Based Machine Learning for Single-Plant Yield Estimation and Trait Prioritization in Faba Bean (Vicia faba L.)
by Yeter Çilesiz, İlkay Yelmen, Tolga Karaköy, Halit Bakır, Seda Karateke and Metin Zontul
Agronomy 2026, 16(17), 1653; https://doi.org/10.3390/agronomy16171653 - 28 Aug 2026
Viewed by 234
Abstract
Faba bean yield reflects complex relationships among genotype, environment, and agronomic traits. This study evaluated an explainable Tabular Prior-data Fitted Network (TabPFN) framework for estimating plot-mean single-plant yield and prioritizing traits using 398 plot-level observations, 13 measured agronomic predictors, and six derived features. [...] Read more.
Faba bean yield reflects complex relationships among genotype, environment, and agronomic traits. This study evaluated an explainable Tabular Prior-data Fitted Network (TabPFN) framework for estimating plot-mean single-plant yield and prioritizing traits using 398 plot-level observations, 13 measured agronomic predictors, and six derived features. On the reference 80/20 split, TabPFN achieved the best values for all four test metrics (R2 = 0.8746, RMSE = 1.9132 g plant−1, MAE = 1.0819 g plant−1, and MAPE = 8.16%). The Friedman test detected differences among the six models (χ2(5) = 16.75, p = 0.005); Nemenyi comparisons distinguished TabPFN from HistGradientBoosting and SVR, whereas the Holm-corrected Wilcoxon analysis confirmed only the TabPFN–SVR difference. Across 10 repeated 80/20 splits, TabPFN obtained the highest mean test R2 (0.8614 ± 0.0691), ranked first in eight splits, and produced a higher R2 than every tuned baseline in at least eight splits. SHAP, permutation importance, and LOCO analyses emphasized pod-, seed-, and biomass-related predictors. Repeated-split ablation showed that derived features improved TabPFN consistently, whereas removing selected target-proximal yield variables reduced performance for every model. The framework is therefore a harvest-time trait-estimation and trait-prioritization tool rather than an early-season forecasting system. Notably, TabPFN achieved this performance without the 100-trial Optuna search used for each baseline; only n_estimators was screened over four prespecified values. Full article
(This article belongs to the Section Precision and Digital Agriculture)
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18 pages, 331 KB  
Article
Personalised Nutraceutical Treatment Guided by MTHFR Genotype in Mental Health: A Retrospective Cohort Study
by Cristina Beer, Fiona Rae, Mikayla Watt, Maciej Trzaskowski, Clarissa Yates, Annalese Semmler and Joanne Voisey
Nutrients 2026, 18(17), 2791; https://doi.org/10.3390/nu18172791 - 26 Aug 2026
Viewed by 321
Abstract
Background & Aims: One-carbon metabolism plays a central role in neurotransmitter synthesis, methylation capacity, and neurobiological resilience. Variants in the methylenetetrahydrofolate reductase (MTHFR) gene can reduce enzymatic activity, affecting folate- and methionine-cycle functions and potentially influencing biological pathways relevant to mood [...] Read more.
Background & Aims: One-carbon metabolism plays a central role in neurotransmitter synthesis, methylation capacity, and neurobiological resilience. Variants in the methylenetetrahydrofolate reductase (MTHFR) gene can reduce enzymatic activity, affecting folate- and methionine-cycle functions and potentially influencing biological pathways relevant to mood and anxiety disorders. Personalised nutraceutical treatment strategies, particularly those addressing methylation capacity through targeted B-vitamin, folate, and adjunctive metabolic interventions are increasingly implemented in integrative clinical practice, yet evidence regarding their clinical outcomes remains limited. Methods: We conducted a retrospective cohort study of 50 adults attending an integrative general practice clinic for anxiety and/or depression. All received personalised nutraceutical treatment informed by clinical assessment, laboratory testing and, for 37/50 patients, MTHFR genotyping. Psychological distress was measured using the Kessler-10 (K10) scale at baseline and approximately three months later. Secondary analyses evaluated whether outcomes differed by MTHFR genotype, whether specific supplements (e.g., L-methylfolate and SAMe) were associated with greater improvement, whether biomarker changes correlated with symptom change, and the safety/tolerability profile. Results: Across the full cohort, mean K10 scores significantly decreased by four points over the treatment period, with 72% of patients showing clinical improvement. Reductions in psychological distress were seen across all MTHFR genotypes, including individuals with homozygous variant genotypes. Supplement-specific analyses showed improvement among those receiving methylfolate or SAMe, although the differences were not statistically significant. Following nutraceutical treatment, biomarker analyses demonstrated significant increases in serum vitamin B12 and modest reductions in homocysteine, but biomarker shifts did not correlate strongly with K10 change. No serious adverse events or clinically significant abnormalities in liver or renal function were identified. Conclusions: In this real-world primary care cohort, personalised nutraceutical treatment, grounded in one-carbon metabolism support and applied alongside usual care, was associated with clinically meaningful reductions in psychological distress. Outcomes were comparable across MTHFR genotypes when treatments were appropriately tailored, suggesting that genotype and biomarker-informed nutraceutical strategies may mitigate potential metabolic disadvantages. These findings support further controlled research into precision nutraceutical psychiatry for anxiety and depression. Secondary analyses of genotype subgroup, specific supplements, and biomarker–outcome associations are reported alongside Benjamini–Hochberg FDR-adjusted p-values and should be interpreted as hypothesis-generating. Full article
(This article belongs to the Section Nutrition and Neuro Sciences)
14 pages, 2800 KB  
Article
Context-Dependent Associations of the APOA1 rs670 Polymorphism with Apolipoprotein A1 and HDL Cholesterol: A Systematic Review and Meta-Analysis
by Chien-Yi Chan, Yi-Chen Huang, Ming-Fen Lee, Chun-Yin Huang and Wen-Chieh Wu
Int. J. Mol. Sci. 2026, 27(17), 7622; https://doi.org/10.3390/ijms27177622 - 25 Aug 2026
Viewed by 222
Abstract
The APOA1 rs670 (−75 G>A) polymorphism has been implicated in lipid metabolism and susceptibility to metabolic syndrome (MetS). However, individual studies have reported inconsistent associations with circulating apolipoprotein A1 (Apo A1) and lipid parameters, and no meta-analysis has comprehensively evaluated these associations stratified [...] Read more.
The APOA1 rs670 (−75 G>A) polymorphism has been implicated in lipid metabolism and susceptibility to metabolic syndrome (MetS). However, individual studies have reported inconsistent associations with circulating apolipoprotein A1 (Apo A1) and lipid parameters, and no meta-analysis has comprehensively evaluated these associations stratified by metabolic disorder status. We therefore quantified the associations between APOA1 rs670 and serum Apo A1 and lipid parameters, and determined whether these associations are modified by metabolic disorder status. PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched from inception to March 2026. Eligible studies reported APOA1 rs670 genotype data with quantitative lipid measurements. Forty studies involving 22,175 participants met the inclusion criteria. Pooled effect sizes were estimated as standardized mean differences (SMDs) with 95% confidence intervals (CIs) using random-effects models. This review was registered in PROSPERO (CRD420261333145). A allele carriers had significantly higher serum Apo A1 (SMD, 0.20; p < 0.001) and HDL-C levels (SMD, 0.14; p < 0.001) than GG homozygotes. Subgroup analyses stratified by metabolic disorder status revealed that the associations with Apo A1 (SMD, 0.53 vs. 0.11) and HDL-C (SMD, 0.23 vs. 0.08) were substantially stronger among individuals with metabolic disorders than among metabolically healthy individuals. No significant associations were observed for LDL-C or triglyceride levels. The APOA1 rs670 polymorphism is associated with higher circulating Apo A1 and HDL-C levels, with stronger associations in individuals with metabolic disorders. These findings suggest that metabolic status modifies the phenotypic effects of rs670 on the Apo A1–HDL pathway. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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19 pages, 1653 KB  
Article
Associations of OPRM1, COMT, and ABCB1 Variants with Opioid Analgesic Response in Acute Renal Colic: A Candidate-Gene Study
by Sıtkı Ün, Ramazan Sabırlı, İbrahim Türkçüer, Gergana Lengerova, Martina Bozhkova, Steliyan Petrov and Aylin Köseler
Pharmaceuticals 2026, 19(9), 1343; https://doi.org/10.3390/ph19091343 - 24 Aug 2026
Viewed by 279
Abstract
Background: Acute renal colic is a common urological emergency characterized by substantial interindividual variability in analgesic response. Pharmacogenetic variation in OPRM1, COMT, and ABCB1 may contribute to differences in opioid efficacy and pain control. This study primarily evaluated the associations [...] Read more.
Background: Acute renal colic is a common urological emergency characterized by substantial interindividual variability in analgesic response. Pharmacogenetic variation in OPRM1, COMT, and ABCB1 may contribute to differences in opioid efficacy and pain control. This study primarily evaluated the associations of OPRM1 A118G (rs1799971), COMT Val158Met (rs4680), and ABCB1 C3435T (rs1045642) polymorphisms with opioid analgesic response in patients with acute renal colic. As a secondary exploratory analysis, genotype and allele frequencies were compared between patients and healthy controls. Methods: This prospective case–control study included 150 patients with acute renal colic and 100 healthy controls. Genotyping was performed using TaqMan SNP Genotyping Assays based on real-time polymerase chain reaction. Genotype frequencies were compared between groups using dominant and recessive genetic models, and Hardy–Weinberg equilibrium was assessed. In addition, genotype–phenotype associations were evaluated using pain severity, early analgesic response, initial opioid dose, rescue analgesic requirement, and multivariable logistic regression analyses. Results: In the secondary exploratory case–control analysis, no statistically significant differences in genotype or allele frequencies of OPRM1 rs1799971, COMT rs4680, or ABCB1 rs1045642 were observed between patients with acute renal colic and healthy controls. Within the patient cohort, however, genotype–phenotype analyses identified differences in early analgesic outcomes. Baseline-adjusted 30 min VAS differed according to OPRM1, COMT, and ABCB1 genotype, with the most pronounced difference observed for ABCB1 rs1045642. Patients with the ABCB1 TT genotype had higher adjusted 30 min VAS scores and showed a pattern of greater opioid requirement and more frequent rescue analgesia. In exploratory multivariable analysis, the ABCB1 TT genotype was associated with higher odds of inadequate early analgesic response (adjusted OR = 2.74, 95% CI 1.18–6.37; p = 0.019). Given the limited number of outcome events, this adjusted association should be considered preliminary and hypothesis-generating. Conclusions: No significant differences in the distributions of the polymorphisms investigated were observed between patients with acute renal colic and healthy controls. Within the patient group, ABCB1 genetic variation was associated with early opioid analgesic response, although this finding should be considered preliminary and requires confirmation in larger prospective pharmacogenetic studies before clinical implementation. Any potential future pharmacogenetic application should be considered as an adjunct to established first-line renal–colic management and specifically in patients for whom opioid therapy is clinically indicated. Full article
(This article belongs to the Section Pharmacology)
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24 pages, 8050 KB  
Article
The First Whole-Genome Characterization of a Kenyan DS-1-like G3P[8] Rotavirus Strain: Evidence for an Intragenogroup Reassortment Event in Africa
by Yuki Akari, Aoko J. Ogutha, Maurine M. Mutua, Mary Wachira, Carlene Sang, Saori Fukuda, Ryoko Shiraishi, James Nyangao, Samoel A. Khamadi, Shingo Inoue, Satoshi Kaneko, Ernest A. Wandera and Satoshi Komoto
Viruses 2026, 18(9), 930; https://doi.org/10.3390/v18090930 - 24 Aug 2026
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Abstract
Unusual DS-1-like G3P[8] rotavirus strains have emerged and spread rapidly across several countries. In Africa, however, reports of these strains and available whole-genome data remain limited, and their evolutionary relationships across the continent are not yet fully understood. In this study, we sequenced [...] Read more.
Unusual DS-1-like G3P[8] rotavirus strains have emerged and spread rapidly across several countries. In Africa, however, reports of these strains and available whole-genome data remain limited, and their evolutionary relationships across the continent are not yet fully understood. In this study, we sequenced and characterized the complete genome of a DS-1-like G3P[8] strain (RVA/Human-wt/KEN/KCH1748/2020/G3P[8]) detected in a child with acute gastroenteritis in Kenya. Strain KCH1748 possessed an unusual genotype constellation: G3-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Phylogenetic analysis revealed that 10 of the 11 genomic segments of strain KCH1748 were closely related to those of other East African DS-1-like G3P[8] strains from Kenya and Tanzania within the globally circulating DS-1-like G3P[8] lineage, suggesting that it may be derived from this globally emerging lineage. In contrast, the VP1 gene of strain KCH1748 was closely related to those of Ghanaian G9P[4] strains, sharing a common branch with Beninese DS-1-like G3P[8] and G2P[4] strains, suggesting a VP1 intragenogroup reassortment event involving African RVA strains. This study provides the first comprehensive whole-genome evolutionary characterization of a DS-1-like G3P[8] strain identified in Kenya. Our findings contribute to understanding the evolutionary dynamics and genomic diversification of emerging DS-1-like G3P[8] strains in Africa. Full article
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10 pages, 559 KB  
Case Report
A Candidate MEST Splice-Site Variant in a Patient with Silver–Russell Syndrome-like Phenotype: First Report and Literature Review
by Xiaocha Xu, Rongrong Pan, Shuai Chen, Fan Yu, Haixia Miao, Kexin Fang, Dingwen Wu, Yi Zhang, Jing Li and Xin Yang
Genes 2026, 17(9), 992; https://doi.org/10.3390/genes17090992 - 24 Aug 2026
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Abstract
Silver–Russell syndrome (SRS) is most commonly caused by epigenetic alterations at 11p15.5 or maternal uniparental disomy of chromosome 7 [upd(7)mat], though other molecular mechanisms remain unclear. While microdeletions encompassing MEST have been associated with SRS-like phenotypes, no pathogenic intragenic MEST variants have been [...] Read more.
Silver–Russell syndrome (SRS) is most commonly caused by epigenetic alterations at 11p15.5 or maternal uniparental disomy of chromosome 7 [upd(7)mat], though other molecular mechanisms remain unclear. While microdeletions encompassing MEST have been associated with SRS-like phenotypes, no pathogenic intragenic MEST variants have been reported to date. We describe a 6-month-old male infant with clinical features suggestive of a SRS-like phenotype, including intrauterine and postnatal growth restriction, triangular facies, prominent forehead, and small extremities. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) revealed neither methylation abnormalities at 11p15.5, 7p13, or 7q32 nor copy number variations (CNVs) in these regions. Trio whole-exome sequencing (trio-WES) identified a paternally inherited splice-site variant (c.890 + 1G > A) in MEST. Given the paternal-specific expression of MEST, this variant resides on the functionally active allele. Based on in silico predictions and clinical correlation, this case identifies MEST as a plausible candidate gene for SRS and provides a rationale for further functional studies. Phenotypic variation exists across molecular subtypes, yet definitive genotype–phenotype correlations await larger, systematically ascertained cohorts. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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23 pages, 2290 KB  
Review
The Role of Monoclonal Antibody Targeted Therapy (Panitumumab) in the Treatment of Metastatic Colorectal Cancer—A Narrative Review of Current Evidence and Emerging Therapeutic Strategies
by Lidia Kwiatkowska and Małgorzata Szczuko
Int. J. Mol. Sci. 2026, 27(17), 7559; https://doi.org/10.3390/ijms27177559 - 24 Aug 2026
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Abstract
Metastatic colorectal cancer (mCRC) remains one of the leading causes of cancer deaths worldwide. Mutations of the RAS and BRAF genes and the location of the primary tumor determine the choice of systemic therapy. Panitumumab—a fully human anti-EGFR monoclonal antibody—is well-established in the [...] Read more.
Metastatic colorectal cancer (mCRC) remains one of the leading causes of cancer deaths worldwide. Mutations of the RAS and BRAF genes and the location of the primary tumor determine the choice of systemic therapy. Panitumumab—a fully human anti-EGFR monoclonal antibody—is well-established in the treatment of patients with wild-type RAS and BRAF and left-sided tumor localization. The aim of this review is to summarize the role and potential of targeted therapies for colorectal cancer with monoclonal antibodies such as panitumumab or cetuximab, to provide current evidence on the position of panitumumab in the treatment of mCRC, and to discuss biomarkers and qualification strategies for targeted therapy, including the role of ctDNA in disease monitoring and rechallenge. The work is based on a narrative review of literature from the PubMed, Scopus, Web of Science and Google Scholar databases, including publications available until May 2026. The efficacy of panitumumab was confirmed in phase III studies: first-line (PRIME: prolongation of OS by 5.6 months) and second-line treatment. A key condition for eligibility is complete RAS and BRAF genotyping, assessment of MSI/dMMR status, HER2 amplification, and tumor location. ctDNA analysis enables monitoring of tumor clonal evolution and qualification for rechallenge—the CHRONOS study showed 30% objective responses with liquid biopsy-based selection. Associations with BRAF/MEK and KRAS G12C inhibitors and modulation of the immune microenvironment via the CCL5/CCR5 axis remain promising directions. Panitumumab occupies an important position in the treatment of patients with mCRC, but increasingly precise molecular stratification and dynamic monitoring of disease with ctDNA are becoming the basis for the effective and rational use of the drug. Unlike reviews that selectively focus on individual aspects of anti-EGFR therapy, the following work integrates all aspects: from molecular biology and biomarkers used to qualify patients to clinical data on panitumumab and new strategies in the fight against mCRC. Further development of next-generation sequencing methods and standardization of ctDNA panels will be crucial for the widespread deployment of targeted therapies in everyday clinical practice. The role of panitumumab is well established in appropriately selected patients with RAS wild-type, particularly left-sided, metastatic colorectal cancer (mCRC). Combining panitumumab with immune checkpoint inhibitors warrants further investigation, particularly in patients with MSS/pMMR mCRC. The observed activity of panitumumab in combination with nivolumab and ipilimumab provides a rationale for further clinical evaluation and monitoring. Full article
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