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22 pages, 2752 KB  
Article
Comparative Genomics Reveals Extensive Biosynthetic Diversity and Lineage-Specific Metabolic Potential Across Talaromyces Species
by Biju Vadakkemukadiyil Chellappan and Hashem Al-Sheikh
J. Fungi 2026, 12(9), 690; https://doi.org/10.3390/jof12090690 - 14 Sep 2026
Abstract
The genus Talaromyces is an important source of structurally diverse secondary metabolites, yet the conservation and diversification of its biosynthetic potential remain incompletely understood at the genus level. Here, we performed comparative genomic and biosynthetic analyses of 24 Talaromyces species to characterize biosynthetic [...] Read more.
The genus Talaromyces is an important source of structurally diverse secondary metabolites, yet the conservation and diversification of its biosynthetic potential remain incompletely understood at the genus level. Here, we performed comparative genomic and biosynthetic analyses of 24 Talaromyces species to characterize biosynthetic gene cluster (BGC) diversity, gene cluster family (GCF) distribution, and potential relevance to antifungal natural-product discovery. Genome mining identified 1550 BGCs, ranging from 41 to 81 per species, with polyketide synthase (PKS), nonribosomal peptide synthetase (NRPS), terpene, and hybrid PKS–NRPS pathways representing the major biosynthetic classes. The BGCs were grouped into 828 GCFs, of which 567 (68.5%) were species-specific, indicating extensive lineage-level diversification. In contrast, several metabolite-associated biosynthetic systems were conserved across multiple species. Notably, squalestatin S1-associated BGCs occurred in all 24 species but were distributed among 15 distinct GCFs, demonstrating conservation of predicted biosynthetic capacity despite substantial variation in cluster architecture. GCFs associated with characterized antifungal metabolites, including ilicicolin H, leucinostatins, zopfiellin, sordarin, and monorden/monocillins, were also identified. Moreover, 553 GCFs (66.8%) lacked close matches to characterized MIBiG clusters and were classified as chemically unresolved, highlighting a substantial unexplored biosynthetic repertoire. Overall, these findings reveal extensive diversification alongside selective conservation of secondary-metabolite pathways across Talaromyces and provide a genomic framework for prioritizing species and BGCs for antifungal natural-product discovery and biocontrol-oriented investigation. These genome-based predictions require metabolomic and functional validation to confirm metabolite production and biological activity. Full article
(This article belongs to the Special Issue Fungal Biosynthesis)
30 pages, 18248 KB  
Article
Aucubin Ameliorates Alloxan-Induced Diabetic Liver Injury in Association with Modulation of the Nrf2/HO-1 Antioxidant Axis and NF-κB-Associated Inflammatory and Apoptotic Signaling
by Amany M. Hamed, Nadia S. Mahrous, Safaa S. Soliman, Lobna A. Ali, Rasha Abdeen Refaei, Olivia N. Beshay, Ahmed S. Osman, Marwan Elsayed Eldeeb Mehana Hamouda, Safaa Mohammed Elmahdy, Samira Mahmoud Mohamed, Zeyad Elsayed Eldeeb Mohana, Mohamed S. A. Gaballah, Elsayed Eldeeb Mehana Hamouda, Aboubakr H. Abdelmonsef and Asmaa A. Hegazy
Int. J. Mol. Sci. 2026, 27(18), 8184; https://doi.org/10.3390/ijms27188184 - 14 Sep 2026
Abstract
Diabetes mellitus is associated with progressive hepatic injury driven by oxidative stress, inflammation, and apoptosis. Aucubin, a natural iridoid glycoside, possesses potent antioxidant and anti-inflammatory activities; however, its hepatoprotective mechanisms in diabetic liver injury remain unclear. This study investigated the protective effects of [...] Read more.
Diabetes mellitus is associated with progressive hepatic injury driven by oxidative stress, inflammation, and apoptosis. Aucubin, a natural iridoid glycoside, possesses potent antioxidant and anti-inflammatory activities; however, its hepatoprotective mechanisms in diabetic liver injury remain unclear. This study investigated the protective effects of aucubin against alloxan-induced diabetic hepatic injury and the underlying molecular mechanisms. Male albino rats were assigned to five groups: normal control, alloxan-induced diabetic, diabetic treated with metformin (150 mg/kg), and diabetic treated with aucubin (25 or 50 mg/kg) for 28 days. We evaluated body weight, fasting blood glucose, liver function, lipid profile, oxidative stress biomarkers, inflammatory cytokines, and hepatic expression of Nrf2, HO-1, NF-κB p65, Bax, and Bcl-2, along with histopathological and immunohistochemical examinations. Alloxan induced marked hyperglycemia, weight loss, hepatic dysfunction, dyslipidemia, oxidative stress, inflammation, and apoptosis. Aucubin significantly ameliorated these alterations, with the 50 mg/kg dose generally showing greater effects than the 25 mg/kg dose. Aucubin improved liver function, ameliorated dyslipidemia, reduced lipid peroxidation, enhanced antioxidant defenses, increased Nrf2 and HO-1 expression, attenuated NF-κB p65 expression and pro-inflammatory cytokines, favorably modulated the Bax/Bcl-2 balance, preserved hepatic architecture, and increased Ki-67 immunoreactivity, indicating enhanced cellular proliferative activity. These findings indicate that aucubin is associated with improved hepatic antioxidant, inflammatory, apoptotic, and metabolic status in alloxan-induced diabetic rats. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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28 pages, 11998 KB  
Article
ShenRongGuBenHuanShao Pill Ameliorates Hydrocortisone-Induced Erectile Dysfunction: Insights from Integrated Multi-Omics Analysis
by Yazhou Shao, Xinqian Song, Yichen Jing, Li Dong, Yanping Wang, Ke Sun and Fangdi Hu
Pharmaceuticals 2026, 19(9), 1456; https://doi.org/10.3390/ph19091456 - 14 Sep 2026
Abstract
Background/Objectives: ShenRongGuBenHuanShao Pill (SRGBHSP) is a traditional Chinese medicine (TCM) used for the treatment of erectile dysfunction (ED). However, its active constituents and pharmacological mechanisms remain unclear. This study characterized the flavonoid constituents of SRGBHSP and investigated its effects on HC-associated ED-related alterations [...] Read more.
Background/Objectives: ShenRongGuBenHuanShao Pill (SRGBHSP) is a traditional Chinese medicine (TCM) used for the treatment of erectile dysfunction (ED). However, its active constituents and pharmacological mechanisms remain unclear. This study characterized the flavonoid constituents of SRGBHSP and investigated its effects on HC-associated ED-related alterations and potential molecular mechanisms using an integrated multi-omics strategy. Methods: SRGBHSP constituents were characterized by UPLC-Q-TOF-MS/MS, and representative flavonoids were quantitatively analyzed by UPLC-MS/MS. Rats exposed to HC received SRGBHSP (1.08, 2.16, or 4.32 g/kg), Yougui Pill, or sildenafil concurrently with HC administration. Pharmacological effects were evaluated using APO-induced erectile responses, histopathology, sperm quality, reproductive hormones, oxidative stress indices, and serum NO/GC/cGMP-related parameters. Integrated 16S rRNA sequencing, untargeted metabolomics, transcriptomics, and DIA-based proteomics were combined with RT-qPCR and Western blotting to investigate potential regulatory mechanisms. Results: A total of 131 flavonoids were characterized in SRGBHSP, including flavones, isoflavones, flavonols, flavanones, chalcones, flavans, anthocyanidins, and aurones. Quantitative analysis identified baicalin as the predominant flavonoid constituent. APO-induced erection frequency decreased from 3.50 ± 1.29 in the control group to 0.50 ± 0.58 in the model group and increased to 4.50 ± 1.29 following high-dose SRGBHSP intervention. SRGBHSP also improved reproductive hormone homeostasis, sperm quality, and oxidative stress status in HC-treated rats. SRGBHSP increased serum NOS, NO, GC, and cGMP levels and increased the mRNA and total protein expression of PI3K, Akt, and mTOR in penile tissue. Integrated multi-omics analyses revealed coordinated alterations in gut microbiota, glycerophospholipid metabolism, and penile transcriptomic and proteomic profiles. Conclusions: SRGBHSP attenuated multiple ED-related alterations associated with HC exposure, accompanied by improvements in reproductive function, oxidative stress status, and serum NO/GC/cGMP-related parameters. Integrated multi-omics analyses together with expression-level validation revealed coordinated alterations in gut microbiota, glycerophospholipid metabolism, and PI3K/Akt/mTOR-related molecules following SRGBHSP intervention. These findings suggest the potential involvement of PI3K/Akt/mTOR-related signaling in the response to SRGBHSP, although its activation status and causal contribution remain to be established. Flavonoids may represent important bioactive constituents associated with the observed effects of SRGBHSP. Overall, this study provides an integrated pharmacological and multi-omics framework for understanding the effects of SRGBHSP on HC-associated ED-related alterations. Full article
(This article belongs to the Section Natural Products)
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23 pages, 4676 KB  
Article
Study of Gut Microbiota Diversity Among Migrant Workers in Jeddah, Makkah Region, Saudi Arabia, Using 16S rRNA Gene Sequencing
by Effat A. Al-Judaibi
Microbiol. Res. 2026, 17(9), 177; https://doi.org/10.3390/microbiolres17090177 - 14 Sep 2026
Abstract
Microbiome diversity varies significantly across countries and social groups due to geographic, ethnic, lifestyle, and dietary factors, with populations in traditional and rural settings tending to harbor more diverse microbial communities than those in industrialized urban environments. In Saudi Arabia, the influx of [...] Read more.
Microbiome diversity varies significantly across countries and social groups due to geographic, ethnic, lifestyle, and dietary factors, with populations in traditional and rural settings tending to harbor more diverse microbial communities than those in industrialized urban environments. In Saudi Arabia, the influx of migrant workers from regions with distinct health and ecological backgrounds represents a public health concern. In particular, these workers may carry novel microbial species from their places of origin, thereby increasing the risk of infectious diseases spreading in the local population. This may also result in disruption of gut microbial homeostasis, thereby elevating risks related to infection, metabolic disorders, and disease susceptibility. Furthermore, the potential emergence of drug-resistant or locally uncommon microbial strains is particularly concerning. In this study, bacterial diversity was assessed in 28 fecal samples collected from migrant workers living in Saudi Arabia, using 16S rRNA gene sequencing targeting the V3–V4 regions. Operational taxonomic units (OTUs) were clustered at 97% sequence similarity, and alpha diversity indices (Shannon, Simpson, Chao1, ACE) were calculated to evaluate microbial richness and evenness. The results revealed considerable inter-individual variability, with Segatella copri, Peptostreptococcus, and Lachnospiraceae identified as dominant taxa across multiple samples. Principal component analysis (PCA) demonstrated distinct patterns of inter-individual variation, indicating compositional heterogeneity within the cohort. Functional predictions using PICRUSt2 suggested enrichment in metabolic pathways related to carbohydrate and amino acid processing. These findings offer a comprehensive characterization of the gut microbiome structure and predicted functionality in a population characterized by diverse geographic origins. Full article
(This article belongs to the Section Microbial Ecology and Microbiomes)
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19 pages, 11689 KB  
Article
Early-Life Stress Programs a Vulnerable Renal Phenotype Under Metabolic Challenge in a Murine Model
by Jhonatan Duque-Colorado and Bélgica Vásquez
Biomolecules 2026, 16(9), 1332; https://doi.org/10.3390/biom16091332 - 14 Sep 2026
Abstract
Early-life stress and post-weaning exposure to a high-fat diet (HFD) have been independently associated with renal abnormalities; however, little is known about how these stressors interact to increase renal susceptibility to subsequent metabolic challenges. Therefore, this study evaluated the effects of early-life stress [...] Read more.
Early-life stress and post-weaning exposure to a high-fat diet (HFD) have been independently associated with renal abnormalities; however, little is known about how these stressors interact to increase renal susceptibility to subsequent metabolic challenges. Therefore, this study evaluated the effects of early-life stress induced by maternal separation (MS) and post-weaning HFD on renal structure and function in male C57BL/6 mice. Animals were subjected to MS or remained unmanipulated (UM) and were subsequently fed a control diet (CD) or HFD until postnatal day 133, generating four experimental groups: UM-CD, UM-HFD, MS-CD, and MS-HFD. Renal structure was assessed by renal mass, histological analysis of the renal corpuscle, stereological quantification of glomerular numerical density (Nv) and individual glomerular volume (IGV), whereas renal function was evaluated by diuresis. MS and HFD independently increased renal mass, altered diuresis, reduced glomerular Nv, and promoted glomerular hypertrophy. Histological analysis revealed mesangial expansion, narrowing of the capsular space, focal capillary obliteration, and glomeruloparietal synechiae, which were pronounced in the MS-HFD group. Two-way ANOVA showed independent effects on Nv and a significant interaction for IGV. Reduced Nv correlated with increased IGV and diuresis. These findings indicate that early-life stress and post-weaning HFD promote complementary mechanisms of glomerular remodeling, increasing susceptibility to metabolically induced renal injury. Full article
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44 pages, 15051 KB  
Review
Cutaneous T Cell Lymphoma: Targeting the Survival Network in Mycosis Fungoides and Sézary Syndrome
by Philipp Heumann, Simon Mehler, Sara Martina Steinmann, Jan P. Nicolay, Martina Müller and Karsten Gülow
Cancers 2026, 18(18), 2956; https://doi.org/10.3390/cancers18182956 - 13 Sep 2026
Abstract
Cutaneous T cell lymphoma (CTCL) comprises a heterogeneous group of skin-homing T cell malignancies, with mycosis fungoides (MF) and Sézary Syndrome representing the most frequent and clinically relevant entities. Their clinical behavior differs substantially: MF often follows an indolent course over years, whereas [...] Read more.
Cutaneous T cell lymphoma (CTCL) comprises a heterogeneous group of skin-homing T cell malignancies, with mycosis fungoides (MF) and Sézary Syndrome representing the most frequent and clinically relevant entities. Their clinical behavior differs substantially: MF often follows an indolent course over years, whereas Sézary Syndrome is a distinct clinicopathological entity that is typically characterized by erythroderma, a high burden of circulating malignant T cells and frequent lymph node involvement. Early-stage MF can often be controlled with skin-directed therapies, but advanced, relapsed or refractory CTCL remains therapeutically challenging. Established treatments are selected primarily according to disease stage, disease compartment and surface-target expression, whereas most pathway-directed, redox-modulating and apoptosis-sensitizing approaches remain investigational. Increasing evidence indicates that malignant T cells are maintained by an interconnected survival network rather than by a single dominant oncogenic pathway. This network includes constitutive inflammatory signaling, nuclear factor kappa B (NF-κB) activation, apoptosis resistance, altered redox homeostasis, mitochondrial and metabolic adaptation, rat sarcoma viral oncogene homolog (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase kinase (MEK) signaling and epigenetic regulation. These mechanisms cooperate to promote malignant T cell survival, therapy resistance, and disease progression, but they also create opportunities for targeted therapeutic intervention. Particular emphasis is placed on redox-regulated cell death, nuclear factor kappa B (NF-κB)-dependent survival, B-cell lymphoma 2 (BCL-2) family proteins, RAS pathway alterations, epigenetic sensitization and mechanism-informed treatment strategies. Integrating clinicopathological staging with molecular profiling and functional vulnerability screens may support more rational combination therapies and improve patient stratification in CTCL. Full article
(This article belongs to the Special Issue Cutaneous Lymphomas: Present and Future)
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15 pages, 2005 KB  
Article
Self-Rated Health Associated with Chronic Diseases and Types of Physical Activity Among Middle-Aged and Older Adults: A Cross-Sectional Study Using Explainable Machine Learning
by Tong Yang, Yongchul Choi, Yonghwan Kim and Munku Song
J. Clin. Med. 2026, 15(18), 7100; https://doi.org/10.3390/jcm15187100 - 13 Sep 2026
Abstract
Background: Self-rated health (SRH) is a widely used indicator reflecting overall physical, psychological, and functional health status. Chronic diseases and physical activity (PA) are associated with SRH in middle-aged and older adults; however, the contribution of chronic disease burden and different types [...] Read more.
Background: Self-rated health (SRH) is a widely used indicator reflecting overall physical, psychological, and functional health status. Chronic diseases and physical activity (PA) are associated with SRH in middle-aged and older adults; however, the contribution of chronic disease burden and different types of PA to SRH requires further investigation. This study investigated the associations of chronic diseases and PA with SRH among middle-aged and older adults. Methods: This cross-sectional study included adults aged ≥40 years who participated in the 2024 Korea National Health and Nutrition Examination Survey (KNHANES), the ninth survey cycle. SRH was classified as poor or favorable based on self-reported health status. Sociodemographic characteristics, chronic diseases, and PA were evaluated using multivariable logistic regression analysis. The reported ORs were adjusted for age, sex, BMI, education level, household income, smoking, alcohol consumption, and employment status. Additional adjustment for other chronic diseases was applied in Model 3 of the overall analysis and in the subgroup analyses. Machine learning was additionally applied to evaluate the contribution of individual predictors to SRH. Model performance was evaluated using the Area Under the Receiver Operating Characteristic curve (AUROC) with five-fold cross-validation. Results: A total of 4079 participants were included, of whom approximately 58.1% were women, and 748 (18.3%) reported poor SRH. Participants with poor SRH were older, had lower income and education levels, and were less likely to meet the aerobic and muscle-strengthening PA guidelines than those with favorable SRH (all p < 0.001). All chronic diseases were significantly associated with poor SRH. Stroke (OR = 2.66, 95% CI = 1.74–4.06) and myocardial infarction or angina (OR = 2.69, 95% CI = 1.91–3.79) showed relatively high ORs, and the likelihood of poor SRH increased progressively with the number of chronic diseases. Participants with three or four chronic diseases had a 7.15-fold higher likelihood of reporting poor SRH than those without chronic diseases (95% CI = 4.63–11.04). Muscle-strengthening PA was related to lower odds of poor SRH (OR = 0.548, 95% CI: 0.435–0.690) and showed consistent inverse associations across most chronic disease groups, whereas aerobic PA showed weaker associations. The XGBoost model showed an AUROC of 0.631 based on five-fold cross-validation. SHAP analysis showed relatively greater contributions of chronic disease burden and household income to the prediction of poor SRH, while muscle-strengthening PA showed a greater contribution than the other PA variables. Conclusions: Chronic diseases and PA were associated with SRH among middle-aged and older adults. The likelihood of poor SRH increased with the number of chronic diseases, whereas muscle-strengthening PA was consistently associated with favorable SRH. These findings suggest that muscle-strengthening PA is associated with favorable SRH among middle-aged and older adults; however, longitudinal studies are needed to further examine this association. Full article
(This article belongs to the Section Geriatric Medicine)
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20 pages, 7090 KB  
Article
Probabilistic–Experimental Assessment of Parametric Reliability of Friction Pairs in Braking Systems of Lifting and Transportation Machinery
by Natalia Fidrovska, Dmytro Volchenko, Ivan Kernytskyy, Ruslan Humeniuk, Andrii Sharybura, Dmytro Zhuravlov, Andrii Voznyi, Oleksandr Vudvud, Oleksandr Semeniy, Anna Markiewicz, Tomasz Wierzbicki, Anna Piętocha and Eugeniusz Koda
Appl. Sci. 2026, 16(18), 9068; https://doi.org/10.3390/app16189068 - 12 Sep 2026
Abstract
This study provides a computational and experimental assessment of the parametric reliability of friction pairs in brake devices for lifting and transport technology. The computational and experimental method for assessing the parametric reliability of various friction units in lifting and transport equipment, based [...] Read more.
This study provides a computational and experimental assessment of the parametric reliability of friction pairs in brake devices for lifting and transport technology. The computational and experimental method for assessing the parametric reliability of various friction units in lifting and transport equipment, based on operational and experimental research data with their permissible dynamic and thermal load of disc-drum and band-shoe brake devices, was developed to evaluate the influence of coupled dynamic and thermal loads on brake friction pair reliability. The operational parameters of the band-shoe brake, considered as a multi-pair friction system, were classified into four functional groups. The external operational parameters of their materials are determined, and the relationship between dynamic and thermal processes, phenomena and effects is established. A new quantitative indicator, the relative coefficient of parameter (RCP), was introduced to characterize the stochastic variability in friction pair performance and to assess parametric reliability. The meaning of parametric reliability for friction pairs is revealed with the subsequent classification of parameters that fit into the structural diagram of its computational and experimental assessment. Based on reliability conditions, the optimal thickness of the transverse or longitudinal section of the metal friction element has been determined, ensuring it does not exceed the permissible level of thermal stress. Experimental investigations of drilling rig winch brakes demonstrated that the RCP values ranged from 0.008 to 0.051 depending on operating conditions. The proposed probabilistic model enables the optimization of metal friction element dimensions while maintaining thermal stresses below critical levels. Full article
(This article belongs to the Section Mechanical Engineering)
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29 pages, 880 KB  
Article
Towards a Neurocognitive Profile of Post-Acute COVID-19: A Longitudinal Study Integrating Subjective Complaints and Computerized Cognitive Testing
by Miroslava Hristova, Radka Massaldjieva, Penka Atanassova and Daniela Kantareva
Brain Sci. 2026, 16(9), 964; https://doi.org/10.3390/brainsci16090964 - 12 Sep 2026
Abstract
Background/Objectives: The relationship between subjective cognitive complaints and objective performance in post-acute COVID syndrome (PACS), and the persistence of objective impairment over extended follow-up, remain unclear. This prospective longitudinal study characterized the neurocognitive profile of PACS by integrating computerized cognitive testing with structured [...] Read more.
Background/Objectives: The relationship between subjective cognitive complaints and objective performance in post-acute COVID syndrome (PACS), and the persistence of objective impairment over extended follow-up, remain unclear. This prospective longitudinal study characterized the neurocognitive profile of PACS by integrating computerized cognitive testing with structured evaluation of subjective complaints across an extended post-infection interval. Methods: A total of 102 adults with a history of COVID-19 infection (3–35 months post-infection; mean age 40.2 ± 10.95 years; 70.6% female) underwent baseline (V1) CogState Battery testing (seven subtests) and structured assessment of persistent post-COVID complaints; 67 participants (65.7%) constituted the matched longitudinal sample and completed the follow-up (V2) after a mean inter-visit interval of 6.69 ± 1.00 months. Domain-specific composites (Attention/Psychomotor function, Learning/Working memory, and two Global indices) were derived from age-adjusted z-scores, with impairment defined as z ≤ −1.5. Results: Persistent complaints were reported by 63.7% of participants at baseline. In the matched longitudinal sample (n = 67) Attention/Psychomotor impairment was the most prevalent and stable finding in the paired sample (65.7% at V1 and 67.2% at V2; McNemar p = 1.000), whereas ONB-defined working-memory impairment declined nominally in the paired sample (39.4% to 24.2%; p = 0.006), although this change did not remain significant after correction for multiple comparisons (BH-FDR q = 0.063). In the baseline sample persistent complaints were associated with poorer objective performance at V1 across all composite indices with small-to-moderate effect sizes (all BH-FDR-adjusted q = 0.042–0.047). These associations were not observed in the follow-up sample at V2. Age was the most robust demographic correlate of impairment, particularly for visuospatial associative memory (CPAL; β = −0.349, p < 0.001); clinical and demographic predictors explained 9.4–13.9% of the variance (R2 = 0.094–0.139) in significant models at Visit 1. Conclusions: Attention/psychomotor dysfunction constituted a persistent objective deficit after COVID-19. Subjective complaints at baseline were associated with objective impairments but did not predict cognitive performance at follow-up. These findings support the use of objective computerized cognitive testing alongside symptom screening in the clinical assessment of post-COVID patients. Interpretation is limited by the absence of pre-COVID cognitive data and of a demographically matched healthy, uninfected control group. Full article
(This article belongs to the Section Cognitive, Social and Affective Neuroscience)
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22 pages, 4483 KB  
Article
Establishment of Serum Cholesterol Sulfate Reference Intervals and Evaluation of Its Diagnostic and Metabolic Associations in Chinese Adults
by Yin Liu, Xucong Ji, Xiaoqian Yu, Hongmei Zhang, Xinhua Dai and Zhiguang Su
Diagnostics 2026, 16(18), 2953; https://doi.org/10.3390/diagnostics16182953 - 12 Sep 2026
Abstract
Background/Objectives: Cholesterol sulfate (CS) is a multifunctional signaling molecule implicated in diverse physiological and pathological processes. Its clinical translation as a biomarker is hindered by the lack of established reference intervals, unclear disease-specific alterations, and undefined relationships with routine laboratory parameters. This study [...] Read more.
Background/Objectives: Cholesterol sulfate (CS) is a multifunctional signaling molecule implicated in diverse physiological and pathological processes. Its clinical translation as a biomarker is hindered by the lack of established reference intervals, unclear disease-specific alterations, and undefined relationships with routine laboratory parameters. This study aimed to establish a serum CS reference range for Chinese populations, evaluate its associations with various diseases and clinical laboratory parameters, and define its clinical diagnostic utility. Methods: A total of 642 subjects were enrolled, comprising 372 healthy controls and 270 patients with one of six diseases: Alzheimer’s disease, osteoporosis, obesity, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), or Crohn’s disease. Serum CS concentrations were quantified using LC-MS/MS. Reference intervals were established using non-parametric methods. Univariate analyses included Spearman’s rank correlation, Mann–Whitney U test, and receiver operating characteristic (ROC) curve analysis; multivariate analysis employed a gamma-family generalized linear model (GLM) with a log-link function, incorporating age, sex, clinical laboratory parameters, and disease status as covariates. The age-by-sex interaction was examined to assess synergistic effects. Incremental diagnostic value of CS was evaluated using the DeLong test and likelihood ratio test. Results: The serum CS reference interval for healthy individuals was 0.55–2.24 mg/L (males: 0.60–2.25 mg/L; females: 0.54–2.20 mg/L), with a significant sex difference. The age-by-sex interaction effect was significant (two-way ANOVA interaction p = 0.005; GLM interaction β = 0.102, p = 0.002). Stratified analysis revealed a significant positive correlation between age and CS in males, but no such association in females. In univariate analysis, CS correlated significantly with total cholesterol (TC), non-HDL-C, hemoglobin A1c (HbA1c), and other biomarkers; CS levels were elevated in Alzheimer’s disease and reduced in Crohn’s disease. In the multivariate GLM, only TC and male sex emerged as independent significant determinants of CS, whereas HbA1c and NAFLD showed borderline effects; no disease group retained independent significance. After adjustment for TC and sex, the residual area under the curves (AUCs) of CS for all diseases were close to 0.50, and DeLong’s test indicated no incremental diagnostic value beyond the baseline model (all p > 0.70). Conclusions: This study is the first to establish a serum CS reference range for the Chinese population. Serum CS levels are independently regulated by TC and sex, with a significant age-by-sex interaction. The associations between CS and disease status were largely mediated by confounding from lipid profiles and age. CS is not suitable as an independent disease biomarker but may serve as a supplementary indicator for assessing lipid metabolism—particularly in male populations, where it may indirectly reflect age-related changes in cholesterol metabolism. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Phenotyping of Metabolic Disorders)
22 pages, 6231 KB  
Article
Bifidobacterium longum B18 Modulates Pharmacologically Induced Sleep Parameters in Rats in Association with Altered Tryptophan–Melatonin Metabolism
by Lili Liang, Qiaoxuan Ke, Lanyan Huang, Shaofang Hu, Weipeng Guo, Weiyi Luo, Ling Chen and Qingping Wu
Foods 2026, 15(18), 3230; https://doi.org/10.3390/foods15183230 - 12 Sep 2026
Abstract
Sleep disorders represent a growing public health concern, yet current pharmacological interventions are limited by tolerance, dependence, and rebound insomnia. This study evaluated the probiotic properties of Bifidobacterium longum B18 and its effects on pharmacologically induced sleep parameters in male Sprague–Dawley rats, focusing [...] Read more.
Sleep disorders represent a growing public health concern, yet current pharmacological interventions are limited by tolerance, dependence, and rebound insomnia. This study evaluated the probiotic properties of Bifidobacterium longum B18 and its effects on pharmacologically induced sleep parameters in male Sprague–Dawley rats, focusing on tryptophan-related metabolism and gut microbiota composition. In vitro, B18 exhibited favourable probiotic characteristics, no detectable haemolytic activity, and susceptibility to all eight antimicrobials tested. In vivo, B18 significantly shortened barbital sodium-induced sleep latency and prolonged pentobarbital sodium-induced sleep duration (p < 0.05). Targeted metabolomic profiling of faeces, plasma, and hippocampus showed increased tryptophan and melatonin concentrations, whereas 5-HTP and 5-HT remained unchanged. B18 was also associated with lower Kyn/Trp ratios, although plasma Kyn concentrations were unchanged. Increased MT/5-HT ratios and elevated hippocampal AANAT levels were also observed, supporting an association with enhanced melatonin-related metabolism. Gut microbiota analysis showed higher abundances of Bifidobacterium and Lactobacillus in the B18 group than in the DZP group, together with lower Desulfovibrio abundance than in the CTR. Exploratory correlation analysis further showed positive associations of Bifidobacterium abundance with faecal tryptophan and melatonin levels and an inverse association with the Kyn/Trp ratio. Collectively, these findings indicate that B. longum B18 modifies pharmacologically induced sleep parameters in association with altered tryptophan–melatonin metabolism and gut microbiota composition, supporting further evaluation of B18 as a candidate probiotic for sleep-related functional applications. Full article
(This article belongs to the Section Nutraceuticals, Functional Foods, and Novel Foods)
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18 pages, 413 KB  
Article
The Role of Communication in Upper Primary Education: A Mixed-Methods Study of School Relationships
by Ágnes Klein and Edina Haslauer
Educ. Sci. 2026, 16(9), 1494; https://doi.org/10.3390/educsci16091494 - 11 Sep 2026
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Abstract
This study examined communication practices in an upper primary school, focusing on interactions among students, teachers, and parents, as well as the role of digital communication in shaping these relationships. The study used a mixed-methods design, integrating quantitative questionnaire data with qualitative, semi-structured [...] Read more.
This study examined communication practices in an upper primary school, focusing on interactions among students, teachers, and parents, as well as the role of digital communication in shaping these relationships. The study used a mixed-methods design, integrating quantitative questionnaire data with qualitative, semi-structured teacher interviews. The sample comprised 50 students, 50 parents, and 25 teachers. The questionnaires explored the frequency, forms, and perceived quality of communication, while the interviews provided deeper insights into the relational and emotional dimensions of communication. The findings indicate that communication is generally perceived as functional and supportive, although its quality and reciprocity vary across stakeholder groups. Students emphasized the importance of teacher support but noted a need for more frequent, meaningful personal interactions. Parents regarded communication as essential but reported only moderate satisfaction with its quality. Teachers identified limited time and the increasing demands of digital communication as the primary barriers to effective interaction. Based on these findings, despite well-established communication structures, schools should strengthen opportunities for reciprocal engagement and interpersonal interaction while maintaining an appropriate balance between digital and face-to-face communication. The findings contribute to a better understanding of school communication dynamics and offer practical implications for developing more effective, relationship-oriented communication practices in upper primary education. Full article
(This article belongs to the Section Education and Psychology)
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21 pages, 686 KB  
Article
Functional and Transcriptional Responses of Neutrophils from Dogs Living Under Different Housing Conditions Following In Vitro Lipopolysaccharide Stimulation
by Marek Kulka, Iwona Monika Szopa, Bartłomiej Różycki and Maciej Klockiewicz
Int. J. Mol. Sci. 2026, 27(18), 8112; https://doi.org/10.3390/ijms27188112 - 11 Sep 2026
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Abstract
Environmental conditions have an impact on animals’ immune systems. Neutrophils, as key components of innate immunity, rapidly respond to bacterial stimuli through the activation of inflammatory and migratory pathways. This study evaluated the transcriptional and functional responses of neutrophils derived from dogs living [...] Read more.
Environmental conditions have an impact on animals’ immune systems. Neutrophils, as key components of innate immunity, rapidly respond to bacterial stimuli through the activation of inflammatory and migratory pathways. This study evaluated the transcriptional and functional responses of neutrophils derived from dogs living under different housing environments following in vitro lipopolysaccharide (LPS) stimulation. Distinct transcriptional profiles were observed among groups in genes associated with leukocyte adhesion (CD11b), chemokine signaling (CXCR1, CXCR2, and CXCL8), and cytokines (TNF-α, IL-1β, and IL-6). Additional cytokine analyses confirmed neutrophil activation and revealed differences in the magnitude and duration of cytokine secretion between groups. These findings indicate that environmental background may be associated with differences in both transcriptional responsiveness and cytokine production in canine neutrophils. Dogs originating from different housing conditions exhibited distinct patterns of inflammatory activation. The combined assessment of gene expression and cytokine secretion provides valuable insight into innate immune adaptation and might represent a useful approach for monitoring immune status in dogs. Full article
29 pages, 1015 KB  
Article
When Attention Fails but Grades Do Not: Attentional Vulnerability, AI Compensation, and Resilience in College Students with ADHD
by Nuphar Avital, Shani Kahta, Menahem Yeari and Dror Malka
Educ. Sci. 2026, 16(9), 1492; https://doi.org/10.3390/educsci16091492 - 11 Sep 2026
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Abstract
Attention-Deficit/Hyperactivity Disorder (ADHD) presents substantial challenges in higher education, including elevated mind wandering, difficulties sustaining attention during academic reading, and diminished self-regulatory capacity. Yet, many students with ADHD achieve academic outcomes comparable to their neurotypical (NT) peers, suggesting that protective and compensatory mechanisms [...] Read more.
Attention-Deficit/Hyperactivity Disorder (ADHD) presents substantial challenges in higher education, including elevated mind wandering, difficulties sustaining attention during academic reading, and diminished self-regulatory capacity. Yet, many students with ADHD achieve academic outcomes comparable to their neurotypical (NT) peers, suggesting that protective and compensatory mechanisms may help decouple attentional vulnerability from distal academic achievement. This study examined whether artificial intelligence (AI) tools may function as compensatory support for college students with ADHD and whether resilience is differentially associated with academic success in this population. A sample of 195 engineering students (ADHD = 84, NT = 111) completed self-report measures of trait mind wandering, boredom proneness, self-efficacy, resilience, return-to-focus ability, AI usage and motivation, alongside Raven’s Progressive Matrices, an academic reading task with attention probes and comprehension questions, and end-of-semester course grades. Students with ADHD reported significantly greater AI usage than NT students (d = 0.32), despite no significant group differences in cognitive ability or course grades. Hierarchical regression showed that once attentional traits were included, diagnostic group membership no longer accounted for AI usage, indicating that attentional vulnerability, particularly elevated mind wandering, rather than diagnosis per se, may better explain AI usage. Self-efficacy was positively associated with AI usage among students with ADHD but not among NT students, though this group difference was not statistically significant; the pattern is therefore reported as tentative rather than as an established compensatory mechanism. Resilience was lower among students with ADHD than among NT students but was not associated with course grade in either group, and neither resilience nor AI usage was independently associated with course grade once cognitive ability and attentional traits were accounted for. These findings suggest that AI use may reflect compensatory academic adaptation to attentional vulnerability in ADHD. More broadly, the results highlight how attentional vulnerability, self-efficacy, AI-based compensatory strategies, and resilience jointly shape academic outcomes in ADHD and raise questions about how equitable, AI-supported learning environments might be designed in higher education. Because the design is cross-sectional, the present data do not establish that AI use improves academic achievement. Full article
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17 pages, 1510 KB  
Article
Graphene Oxide Multilayers with Violet-Blue Luminescence Fabricated Through Controlled Oxidation at 275 K
by Olga Lucero Illescas-Sánchez, José Alberto Luna López, Yosemik Arjuna León Nataret, Karim Monfil Leyva, Gabriel Omar Mendoza Conde, Javier Flores Méndez, José Álvaro David Hernández de la Luz, Mario Moreno Moreno, Erick Gastellóu Hernández and Zaira Jocelyn Hernández Simón
Coatings 2026, 16(9), 1083; https://doi.org/10.3390/coatings16091083 - 11 Sep 2026
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Abstract
Synthesis of multilayer graphene oxide (GO) was achieved through a Hummers method with meticulous control over the addition of the oxidizing agent. Precursors were immersed in an ice bath during the synthesis to maintain a temperature of approximately 275 K in oxidation stages [...] Read more.
Synthesis of multilayer graphene oxide (GO) was achieved through a Hummers method with meticulous control over the addition of the oxidizing agent. Precursors were immersed in an ice bath during the synthesis to maintain a temperature of approximately 275 K in oxidation stages I and II, temperature was measured with a thermocouple inside the cooling bath, in direct contact with the vacuum filter flask at the level of the reactants. In contrast to the variety of Hummers synthesis methods—where the system is maintained at certain temperature during the initial oxidation stage and heat continues to be supplied during the second stage—our setup operates at low temperature from the beginning to the conclusion of the process. A detailed analysis of the compositional, structural, and optical properties of the fabricated GO was conducted, revealing a notable photoluminescent band in the 380–480 nm region. This property is of interest for a potential future application in the field of optoelectronics. X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM) revealed that the structure of the material consists of a sp3 matrix with sp2 domains. Raman spectroscopy revealed an ID/IG ratio of 2.7, which could indicate a high density of structural defects or extremely small sp2 graphitic domains. Furthermore, deconvolution of the 2D band suggests the presence of multilayers in the GO. Fourier transform infrared spectroscopy (FTIR) analysis revealed the presence of all functional groups associated with the GO. Upon observation of the photoluminescence exhibited by the material, a broadband centered on the violet-blue emission, with a possible mechanism consistent with the literature associated with the transitions between sp2 domains and localized states in the basal plane defects or it might be caused by quantum confinement effects. The diminished contribution from the green emission could be caused by the transitions between localized states sp2 and the functional groups associated with oxygen. Full article
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