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21 pages, 2814 KB  
Article
Gamma-Glutamyl Transferase and Cognitive Outcomes: A Cross-Species Analysis and Hepatic Transcriptomic Signature
by Rongjiang Zhang, Tianhao Yu, Kai Hao, Hui Lu, Wenting Zhang, Ying Yu, Lingxiao Chen and Xiaorui Cheng
Life 2026, 16(10), 1735; https://doi.org/10.3390/life16101735 - 16 Oct 2026
Abstract
Cognitive impairment is a major public health concern, and the liver–brain axis has attracted growing interest. Gamma-glutamyl transferase (GGT) is a serum marker of liver function, but its association with cognitive outcomes remains uncertain. We conducted a cross-species analysis. In 5xFAD mice ( [...] Read more.
Cognitive impairment is a major public health concern, and the liver–brain axis has attracted growing interest. Gamma-glutamyl transferase (GGT) is a serum marker of liver function, but its association with cognitive outcomes remains uncertain. We conducted a cross-species analysis. In 5xFAD mice (n = 52), we examined serum liver markers and spatial cognition using the Morris water maze. In NHANES 2011–2014 (n = 3181, aged ≥60 years), we evaluated liver markers and low cognitive performance (LCP) using multivariable logistic regression. We also performed virtual hepatic GGT1 knockout in a human liver single-cell atlas and integrated GTEx liver co-expression, transcription factor enrichment, and WGCNA analyses. In mice, GGT–cognition associations largely attenuated after strain adjustment, but a positive association with platform crossings emerged (r = 0.321, p = 0.02). In NHANES, serum GGT was inversely associated with LCP (Q4 vs. Q1 OR = 0.54, p < 0.001), with a nonlinear association and an inflection point near 19 U/L. Virtual hepatic GGT1 knockout identified eight immunoglobulin-related genes associated with SPI1 and oxidative stress-related pathways. These parallel findings are hypothesis-generating. A testable hypothesis is that lower hepatic GGT1 activity or serum GGT is associated with upregulated cholangiocyte immunoglobulin-related programs and poorer cognition. Full article
(This article belongs to the Section Epidemiology)
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13 pages, 780 KB  
Article
Natural History and Clinical Outcomes of HBeAg-Negative Chronic Hepatitis B Patients in the “Grey Zone”: A Longitudinal Cohort Study
by Yunling Xue, Mengyuan Liu, Guorui Wang, Qiao Tang, Jingsong Wang, Jing Zhang, Yi Zeng, Mingli Peng, Xiaoqing Liu and Peng Hu
J. Clin. Med. 2026, 15(20), 7832; https://doi.org/10.3390/jcm15207832 - 10 Oct 2026
Viewed by 144
Abstract
Introduction and Objectives: Up to one-third of treatment-naïve, HBeAg-negative chronic hepatitis B (CHB) patients with normal ALT do not meet the strict criteria for the inactive carrier (IC) phase, falling into a “Grey Zone” (GZIC). We aimed to delineate the longitudinal outcomes of [...] Read more.
Introduction and Objectives: Up to one-third of treatment-naïve, HBeAg-negative chronic hepatitis B (CHB) patients with normal ALT do not meet the strict criteria for the inactive carrier (IC) phase, falling into a “Grey Zone” (GZIC). We aimed to delineate the longitudinal outcomes of GZIC patients compared with strictly defined IC patients. Patients and Methods: This retrospective cohort study included 386 HBeAg-negative, ALT-normal CHB patients (125 GZIC, 261 IC). Endpoints included phase transition to immune-active stages, antiviral initiation, and end-stage liver disease (cirrhosis or hepatocellular carcinoma (HCC)). Cumulative incidence was assessed using Kaplan–Meier analysis. Results: Over a median follow-up of 4.5 years, the GZIC cohort exhibited significantly higher cumulative incidence of phase transition (36.8% vs. 13.8%, p < 0.001), antiviral initiation (37.6% vs. 18.8%, p = 0.00014), and end-stage liver disease (4.8% vs. 1.5%, p = 0.049) compared with the IC cohort. All incident HCC cases occurred exclusively in the GZIC group. Multivariate analysis identified baseline GZIC status, male sex, and elevated AFP as independent risk factors. A lower ALT cutoff of 24.5 U/L was superior to 40 U/L in predicting phase transition (p < 0.01). Sex-stratified analyses confirmed that GZIC remained an independent risk factor for phase transition in both male and female patients (both p < 0.05). Conclusions: The GZIC phase is not a benign state. Compared with true inactive carriers, GZIC patients face a significantly elevated risk of progression and liver-related complications, supporting proactive surveillance and timely antiviral intervention. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
18 pages, 1389 KB  
Article
IncobotulinumtoxinA for Upper Limb Essential Tremor: A Randomized, Double-Blind, Placebo-Controlled Trial
by David M. Simpson, Marta Banach, Jason Aldred, Jack Lee, William Ondo, Fernando Pagan, Anastasia Bagretsova, Gudrun Klein, Thorin L. Geister, Irena Pulte and Mandar Jog
Toxins 2026, 18(10), 435; https://doi.org/10.3390/toxins18100435 - 9 Oct 2026
Viewed by 122
Abstract
This double-blind, placebo-controlled, phase II trial (NCT04766723) investigated the efficacy and safety of incobotulinumtoxinA (Xeomin®) in the treatment of essential tremor (ET) of the upper limb (UL). Adults with ET of the UL were randomized 2:1 (n = 78) and [...] Read more.
This double-blind, placebo-controlled, phase II trial (NCT04766723) investigated the efficacy and safety of incobotulinumtoxinA (Xeomin®) in the treatment of essential tremor (ET) of the upper limb (UL). Adults with ET of the UL were randomized 2:1 (n = 78) and treated (n = 77) with intramuscular injections of incobotulinumtoxinA or placebo at semi-flexible doses into their motor-dominant arm. The primary endpoint was the change from baseline to week 6 in maximum tremor amplitude at wrist level. Baseline characteristics of treated patients were well matched across treatment arms. The primary endpoint was not met; maximum tremor amplitude at the wrist decreased from baseline to week 6 in both groups, with changes numerically favoring placebo (least squares mean treatment difference 0.21, p = 0.28). At week 6, compared with the placebo group, the incobotulinumtoxinA group had improvement in The Essential Tremor Rating Assessment Scale (TETRAS) performance dominant UL score (p = 0.006) and Quality of Life in ET (QUEST) total score (p = 0.073). However, these secondary outcomes must be interpreted descriptively as exploratory findings. Although the p-value and the 95% confidence interval including zero did not support statistical significance, the observed numerical treatment difference in change from baseline in QUEST total score suggests that the treatment effect may be consistent with the minimal clinically important difference in favor of incobotulinumtoxinA. Improvement in TETRAS Activities of Daily Living UL score was similar in both groups at week 6 (p = 0.933). IncobotulinumtoxinA was generally well tolerated. Treatment of UL ET with incobotulinumtoxinA did not show superiority over placebo for the primary endpoint. Secondary and other efficacy endpoints should therefore be viewed as exploratory, generating hypotheses suggesting potential improvements in TETRAS UL performance score and quality of life that require confirmation in further research. IncobotulinumtoxinA demonstrated a favorable safety profile without any new or unexpected safety concerns. Full article
(This article belongs to the Section Bacterial Toxins)
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20 pages, 11873 KB  
Article
Circulating Pro-Resolving Mediators Maresin-1 and Maresin-2 and Adipolin/CTRP12 in Adults with Atopic Dermatitis: A Case–Control Study
by Mahir Dığış, Kısmet Kaya, Betül Demir, Zeynep Hilal Gündüz, Kadir Ceren, Ahmet Furkan Süner and Süleyman Aydın
Medicina 2026, 62(10), 1923; https://doi.org/10.3390/medicina62101923 - 6 Oct 2026
Viewed by 170
Abstract
Background and Objectives: Defective resolution of inflammation may contribute to chronicity in atopic dermatitis (AD). Maresin-1 (MaR1) and Maresin-2 (MaR2) are docosahexaenoic acid-derived specialised pro-resolving mediators, and adipolin/C1q/TNF-related protein 12 (CTRP12) is an adipokine with anti-inflammatory properties; to our knowledge, none has been [...] Read more.
Background and Objectives: Defective resolution of inflammation may contribute to chronicity in atopic dermatitis (AD). Maresin-1 (MaR1) and Maresin-2 (MaR2) are docosahexaenoic acid-derived specialised pro-resolving mediators, and adipolin/C1q/TNF-related protein 12 (CTRP12) is an adipokine with anti-inflammatory properties; to our knowledge, none has been evaluated in the circulation of patients with AD. Materials and Methods: In this single-centre case–control study, 44 adults with AD and 44 healthy controls were enrolled. Serum MaR1, MaR2, and adipolin were measured by enzyme-linked immunosorbent assay, and disease severity was graded with the Scoring Atopic Dermatitis (SCORAD) index and the Eczema Area and Severity Index (EASI). Between-group comparisons were complemented by covariate-adjusted models (age, sex, body mass index, smoking), Spearman correlation, receiver operating characteristic (ROC) analysis, and false discovery rate control. Results: Serum adipolin (3.16 vs. 3.23 ng/mL; p = 0.211), MaR1 (140.31 vs. 141.09 ng/L; p = 0.815), and MaR2 (67.56 vs. 72.29 pg/mL; p = 0.512) did not differ between patients and controls, and the null findings persisted after adjustment (all p ≥ 0.306). None of the three biomarkers correlated with SCORAD or EASI (all p ≥ 0.389) or discriminated patients from controls (area under the ROC curve 0.459–0.578). Results were unchanged when measurements outside the assay calibration ranges (adipolin, 67.0% below; MaR1, 14.8% and MaR2, 13.6% above) were censored. Serum lactate dehydrogenase was higher in patients (217.52 vs. 183.39 U/L; q = 0.004) and correlated with SCORAD (ρ = 0.404) and EASI (ρ = 0.349). Adipolin and MaR1 were strongly correlated (ρ = 0.815), including among samples with adipolin below the calibration range (ρ = 0.640). Conclusions: Circulating MaR1, MaR2, and adipolin/CTRP12 were not altered in adults with AD and do not appear useful as standalone diagnostic or severity biomarkers, although compartmentalised cutaneous activity cannot be excluded. The adipolin–MaR1 correlation showed features of an analytical artefact and should not be interpreted biologically. Full article
(This article belongs to the Section Dermatology)
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16 pages, 1270 KB  
Article
Clinical and Biological Factors Associated with Pseudoprogression Under Immune Checkpoint Inhibitors: A Retrospective Pan-Tumor Cohort Study
by Amélie Toulet, Valérie Seegers, Frédéric Bigot, Sylvère Guillemois, Damien Vansteene, Rémy Delva and Manon de Vries-Brilland
Cancers 2026, 18(18), 3040; https://doi.org/10.3390/cancers18183040 - 19 Sep 2026
Viewed by 339
Abstract
Background: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but may induce pseudoprogression (PP), an atypical response pattern that may mimic progressive disease (PD). Although iRECIST criteria were developed to characterize such atypical responses, distinguishing PP from PD when progression is first [...] Read more.
Background: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but may induce pseudoprogression (PP), an atypical response pattern that may mimic progressive disease (PD). Although iRECIST criteria were developed to characterize such atypical responses, distinguishing PP from PD when progression is first observed remains challenging. We aimed to characterize patients with clinically suspected PP and explore clinical and biological factors associated with subsequent classification as PP versus PD. Methods: We conducted a retrospective single-center study including patients with metastatic cancer treated with ICIs at the Institut de Cancérologie de l’Ouest (ICO) in whom PP was clinically suspected. Clinical, biological, treatment, and outcome data were collected at ICI initiation, PP suspicion, and subsequent PP/PD classification. Associations with PP versus PD were explored using univariable and multivariable logistic regression. Results: Among 123 patients with clinically suspected PP, 56 were subsequently classified as PP and 67 as PD. The most frequent primary tumors were lung (38%), kidney (24%), and bladder (11%) cancers. Median time from ICI initiation to PP suspicion was 79 days. ECOG performance status of 0 at ICI initiation was more frequent in the PP than in the PD group (55% vs. 32%; p = 0.046). At PP suspicion, median LDH levels were lower in the PP than in the PD group (189 vs. 232.5 U/L; p = 0.003). After multivariable adjustment, higher LDH levels at PP suspicion remained associated with PD (adjusted OR 2.78 per 100 U/L increase; 95% CI, 1.19–6.52; p = 0.019). Conclusions: In patients with clinically suspected PP, LDH may provide complementary information but cannot reliably distinguish PP from PD when considered alone. Confirmatory imaging therefore remains essential for treatment decision-making. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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12 pages, 245 KB  
Article
Identifying MASLD Patients with MASH or Significant Fibrosis: The Role of Lower ALT Thresholds
by Ying Ma, Hang Yang, Yuanyuan Zhao, Ping Han, Yuying Jin, Lili Zhao, Jie Liu and Jia Li
J. Clin. Med. 2026, 15(18), 7212; https://doi.org/10.3390/jcm15187212 - 17 Sep 2026
Viewed by 259
Abstract
Background: Serum ALT is widely used to assess liver inflammation and fibrosis, yet metabolic steatohepatitis (MASH) and significant fibrosis can still occur in metabolic dysfunction-associated steatotic liver disease (MASLD) patients with normal ALT. However, liver histology in patients with ALT below the cutoffs [...] Read more.
Background: Serum ALT is widely used to assess liver inflammation and fibrosis, yet metabolic steatohepatitis (MASH) and significant fibrosis can still occur in metabolic dysfunction-associated steatotic liver disease (MASLD) patients with normal ALT. However, liver histology in patients with ALT below the cutoffs remains poorly characterized. This study aimed to compare the diagnostic performance of conventional and lower ALT thresholds for assessing MASH and significant fibrosis, using liver biopsy as the reference standard. Materials: This retrospective cross-sectional, two-center study included 404 patients with MASLD, without concurrent viral hepatitis, who underwent liver biopsy at two hospitals in Tianjin between October 2012 and October 2024. The assessment of inflammation and fibrosis was based on liver biopsy histology. Patients were stratified using both conventional and lower ALT thresholds (30 U/L for men, 19 U/L for women). Results: Among the 404 patients, 70.3% had MASH and 67.1% had significant fibrosis. Of those with conventionally normal ALT levels (n = 130), the prevalence of MASH and significant fibrosis was 49.23% and 50.00%, respectively. Using a lower ALT threshold, patients with ALT between the conventional and lower thresholds had significantly higher rates of significant fibrosis compared to those with ALT below the lower threshold (56.18% vs. 36.59%, p = 0.002). The incidence of MASH also showed a decreasing trend in the lower ALT group (53.93% vs. 39.02%, p = 0.082). Multivariate analysis showed that the application of a lower ALT ULN was independently associated with MASH (OR = 5.188, 95% CI: 1.494–18.018, p < 0.001). Conclusions: The study evaluated the association between liver histology and ALT under alternative externally proposed ALT thresholds. The lower ALT threshold was independently associated with MASH, but its diagnostic performance was limited; further prospective evaluation is warranted. Full article
(This article belongs to the Section Endocrinology & Metabolism)
14 pages, 410 KB  
Article
Are Selenium Status and Inflammation Linked to Cardiometabolic Risk Factors in Inborn Errors of Immunity?
by Rosana Gomes de Torres Rossi, Lucila Pereira, Fabíola Isabel Suano-Souza, Itana Gomes Alves Andrade, Rogério do Prado, Carolina Sanchez Aranda, Agatha Nogueira Previdelli, Roseli Oselka Saccardo Sarni and Maria Teresa Terreri
Nutrients 2026, 18(18), 3030; https://doi.org/10.3390/nu18183030 - 16 Sep 2026
Viewed by 286
Abstract
Background/Objective: Patients with Inborn Errors of Immunity (IEI) are at increased cardiometabolic risk due to inflammation, immune dysfunction, and oxidative stress. Given selenium’s essential role in antioxidant defense, this study evaluated plasma selenium concentration in individuals with IEI and its associations with inflammatory [...] Read more.
Background/Objective: Patients with Inborn Errors of Immunity (IEI) are at increased cardiometabolic risk due to inflammation, immune dysfunction, and oxidative stress. Given selenium’s essential role in antioxidant defense, this study evaluated plasma selenium concentration in individuals with IEI and its associations with inflammatory and metabolic biomarkers and body mass index (BMI). Methods: A controlled cross-sectional study involved 85 patients, 22 with ataxia–telangiectasia (A-T), 32 with common variable immunodeficiency (CVI) and 31 with juvenile systemic lupus erythematosus (jSLE). The control group comprised 72 age- and sex-matched healthy individuals. Anthropometric, inflammatory, metabolic, and oxidative stress parameters were assessed, including BMI, ultrasensitive C-reactive protein (usCRP), lipid profile, fasting glucose, insulin, plasma Se concentrations, erythrocyte glutathione peroxidase (GPx) activity, and malondialdehyde levels. Results: Selenium concentrations below the reference value (46 µg/L) were observed in all groups, A-T (41%), CVI (50%), jSLE (48%) and the control group (33%). Low weight was more frequent in the A-T group (41%), whereas excess weight predominated in the CVI (47%) and jSLE (19%) groups. Multiple linear regression showed lower selenium concentrations in the jSLE (β = −10.1 ug/L) and CVI (β = −12.8 µg) groups compared with the controls (p < 0.05). Selenium concentrations were associated with age (β = 0.3 µg/L) and usCRP (p < 0.05). The GPx values were lower among all patient groups (jSLE: β = 3228 U/L, A-T: β = −2030 U/L, and CVI: β = −2060 U/L) (p < 0.05) compared with the controls. The GPx was also influenced by age (β = 56 U/L; p = 0.010). Conclusion: The present findings suggest alterations in the endogenous antioxidant defense system in patients with IEI, characterized by reduced erythrocyte GPx activity and lower plasma selenium concentrations. The inverse association between selenium and usCRP concentrations suggests a potential link between selenium status and systemic inflammation. However, these findings should be interpreted cautiously, as inflammation may influence circulating selenium concentrations, and the cross-sectional design does not establish causal inferences. Further longitudinal studies are warranted to clarify the relationship between selenium status, inflammation, and antioxidant defense in IEI. Full article
(This article belongs to the Special Issue Advances in Nutrition for Autoimmune and Inflammatory Diseases)
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26 pages, 799 KB  
Article
The Inclusion of Supercritical Fluid Extract of Ulva lactuca in the Diet of Common Carp (Cyprinus carpio) Enhances Physiological Resilience and Antioxidant Status During Therapeutic-Dose Antibiotic Administration
by Alina Nicoleta Macoveiu (Dobre), Liliana Mihalcea, Dana Moraru, Nicoleta Bălan, Mirela Crețu, Angelica Docan, Iulia Grecu, Cristian Rîmniceanu, Daniela Ionela Istrati, Floricel Maricel Dima and Lorena Dediu
Antioxidants 2026, 15(9), 1171; https://doi.org/10.3390/antiox15091171 - 15 Sep 2026
Viewed by 381
Abstract
The widespread use of antibiotics in aquaculture has raised concerns regarding adverse physiological effects on fish, creating a need for dietary strategies that enhance fish resilience during antibiotic administration and support animal welfare under therapeutic treatment conditions. This study evaluated, for the first [...] Read more.
The widespread use of antibiotics in aquaculture has raised concerns regarding adverse physiological effects on fish, creating a need for dietary strategies that enhance fish resilience during antibiotic administration and support animal welfare under therapeutic treatment conditions. This study evaluated, for the first time, a phytochemically characterized supercritical fluid extract of Ulva lactuca (Ul-SFE), rich in flavan-3-ols (epigallocatechin, epicatechin gallate) and other phenolics, as a dietary supplement in common carp (Cyprinus carpio). Juvenile carp (n = 360; 20.20 ± 0.13 g) received a control or Ul-SFE-supplemented diet (50 mg kg−1) for 10 weeks, followed by 10 days of florfenicol or oxytetracycline exposure at therapeutic doses. Growth, plasma biochemistry, oxidative stress, and innate immunity were assessed. Ul-SFE significantly improved FCR, SGR, and PER during growth. Under antibiotic challenge, both florfenicol and oxytetracycline affected growth performance and biochemical status, though with different predominant patterns: florfenicol exposure was mainly characterized by reduced growth performance, while oxytetracycline exposure was mainly characterized by biochemical disturbance—reduced total protein and globulin, elevated glucose, ALT, and lipid peroxidation, and impaired antioxidant/immune status. Ul-SFE consistently attenuated these effects, reducing malondialdehyde by 24–30% and increasing antioxidant capacity by 5–7%; its protective effect on lysozyme was strongly diet-dependent (Diet × Antibiotic, p < 0.001), ranging from a 20% increase without antibiotics to negligible under oxytetracycline. These findings show Ul-SFE improves feed utilization and confers partial, treatment-dependent resilience against antibiotic-induced stress, supporting its potential as a functional feed additive in aquaculture. Full article
(This article belongs to the Special Issue Oxidative Stress and Antioxidant Defenses in Aquatic Animals)
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20 pages, 927 KB  
Article
Pathological Complete Response and Residual Disease Patterns After Neoadjuvant Chemoradiotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma: Clinical and Laboratory Associations
by Azer Gökmen and Erdoğan Şeyran
Cancers 2026, 18(18), 2983; https://doi.org/10.3390/cancers18182983 - 15 Sep 2026
Viewed by 272
Abstract
Background: Pathological response after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma may differ between the primary tumor and regional lymph nodes. We evaluated pretreatment factors associated with pathological complete response (pCR) and the anatomical distribution of residual disease after esophagectomy. Methods: This retrospective [...] Read more.
Background: Pathological response after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma may differ between the primary tumor and regional lymph nodes. We evaluated pretreatment factors associated with pathological complete response (pCR) and the anatomical distribution of residual disease after esophagectomy. Methods: This retrospective single-center cohort included 100 patients treated with neoadjuvant chemoradiotherapy followed by esophagectomy. pCR was defined as ypT0N0. Associations with pCR were evaluated using logistic regression. Results: Among 99 response-evaluable patients, 59 achieved pCR (59.6%; 95% CI, 49.7–68.7%). Of 40 patients with non-pCR, residual disease involved only the primary tumor in 26 (65%), both primary and nodal compartments in 10 (25%), and only regional lymph nodes despite complete primary tumor regression in 4 (10%). Overall, 14 patients with non-pCR (35%) had residual nodal disease. In an exploratory adjusted analysis that could not account for baseline cT and cN categories, lower pretreatment lactate dehydrogenase (OR per 10 U/L increase, 0.93; 95% CI, 0.86–0.99; p = 0.026) and female sex (OR, 2.72; 95% CI, 1.02–7.24; p = 0.045) were associated with pCR. Conclusions: Response was heterogeneous across primary tumor and nodal compartments. Primary tumor regression did not invariably indicate nodal clearance, supporting compartment-specific response assessment. The lactate dehydrogenase and sex associations may reflect residual confounding by baseline disease extent and require external validation. Full article
(This article belongs to the Special Issue Advances in Clinical Therapy and Prognosis of Gastrointestinal Cancer)
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14 pages, 269 KB  
Article
Evaluation of Liver Biomarker Levels in Farmers Occupationally Exposed to Pesticides: A Cross-Sectional Study
by Hung The Dang, Thoa Phuong Nguyen, Thu Thi Yen Pham, Chinh Thi Luu, Ha Thi Thu Nguyen, Oanh Thi Kieu Nguyen, Oanh Thi Phuong Ngo, Chinh Thi Tuyet Do, Ha Thi Ngoc Bui and Quan Hong Duong
Diseases 2026, 14(9), 337; https://doi.org/10.3390/diseases14090337 - 14 Sep 2026
Viewed by 306
Abstract
Background/Objectives: Occupational pesticide exposure is a recognized hepatotoxic hazard; however, biomonitoring data characterizing liver function among Vietnamese agricultural workers remain scarce. This study compared serum hepatic biomarkers between pesticide-exposed fruit farmers (exposed group) and a non-exposed reference group (unexposed group) in a northern [...] Read more.
Background/Objectives: Occupational pesticide exposure is a recognized hepatotoxic hazard; however, biomonitoring data characterizing liver function among Vietnamese agricultural workers remain scarce. This study compared serum hepatic biomarkers between pesticide-exposed fruit farmers (exposed group) and a non-exposed reference group (unexposed group) in a northern province in Vietnam, and evaluated whether biomarker alteration varied with cumulative exposure duration. Methods: A cross-sectional study using convenience sampling was conducted from April to October 2022 among 150 adults, comprising 100 fruit farmers with ≥1 year of direct occupational pesticide exposure and 50 unexposed controls. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total and indirect bilirubin, alpha-fetoprotein (AFP), and glucose were quantified using clinical laboratory assays. Multivariable linear regression models, adjusting for age, sex, and body mass index (BMI), were used to evaluate associations between pesticide exposure duration and biomarker levels. Results: Pesticide-exposed farmers had significantly higher mean concentrations of ALT (28.88 vs. 22.36 U/L, p = 0.002), AFP (3.06 vs. 1.16 ng/mL, p < 0.001), total bilirubin (9.93 vs. 7.74 μmol/L, p < 0.001), and indirect bilirubin (8.40 vs. 5.26 μmol/L, p < 0.001) than unexposed controls. While mean AST did not differ (p = 0.105), the proportion of abnormal AST cases was significantly higher among exposed individuals (23% vs. 8%, p = 0.043). After adjustment for age, sex, and BMI in multivariable linear regression models, prolonged exposure (>10 years) remained modestly associated with higher AFP and bilirubin levels (p < 0.05), while associations with ALT and AST were not statistically evident (p > 0.05). Conclusions: These findings suggest a possible association between occupational pesticide exposure and subclinical hepatic alterations, supporting calls for regular health surveillance and enhanced protective measures among fruit farmers. Full article
27 pages, 13530 KB  
Article
Preparation, Characterisation, and Fresh-Keeping Application of Pullulan/Konjac Glucomannan/Low-Acyl Gellan Gum Ternary Edible Composite Films for Extending the Shelf Life of Plums
by Peng Huang, Lei Cao, Mingzhen Li, Fang Wu, Yujia Xia, Shuyi Li, Tongtong Ye, Shuxin Peng, Lin Ye, Pinyao Zhao and Wen Qin
Foods 2026, 15(18), 3235; https://doi.org/10.3390/foods15183235 - 13 Sep 2026
Viewed by 261
Abstract
The escalating environmental burden of conventional plastic food packaging has intensified the search for sustainable, biodegradable alternatives. However, single-component polysaccharide edible films often exhibit suboptimal mechanical and barrier properties, which limits their practical applicability. In this study, pullulan (PUL), konjac glucomannan (KGM) and [...] Read more.
The escalating environmental burden of conventional plastic food packaging has intensified the search for sustainable, biodegradable alternatives. However, single-component polysaccharide edible films often exhibit suboptimal mechanical and barrier properties, which limits their practical applicability. In this study, pullulan (PUL), konjac glucomannan (KGM) and low-acyl gellan gum (LGG) were blended as film-forming substrates with glycerol as a plasticiser. Single-factor experiments combined with Box–Behnken response surface methodology (RSM) were employed to optimise the formulation of ternary edible composite films. The effects of PUL, KGM and LGG concentrations on mechanical properties and water vapour permeability (WVP) were systematically investigated. The optimised film was comprehensively characterised for microstructure, physical barrier performance, antioxidant activity, soil disintegration, bacteriostatic capacity and plum preservation efficiency. The optimal formulation comprised 1.43 g/100 mL PUL, 0.24 g/100 mL KGM and 0.48 g/100 mL LGG. Under these conditions, the composite film exhibited a transparent and smooth appearance, with a continuous and dense internal microstructure. The comprehensive performance score (K) reached 0.805 ± 0.013, with a WVP of 2.75 ± 0.17 g·μm/(m2·h·kPa), light transmittance of 89.93% ± 1.26%, tensile strength (TS) of 3.05 ± 0.14 N/cm2, elongation at break (EB) of 64.57% ± 0.58% and DPPH radical scavenging activity of 34.12% ± 0.96%. Storage trials on two plum varieties demonstrated that the composite coating effectively mitigated fruit weight loss, retarded peel browning and pulp softening, and maintained superior sensory quality throughout storage. Overall, the PUL/KGM/LGG ternary edible composite film exhibited favourable mechanical strength, promising water vapour barrier properties and moderate antioxidant activity, suggesting its potential as a useful reference for the further development and industrial adoption of biodegradable edible films in fruit and vegetable preservation. Full article
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18 pages, 826 KB  
Article
The Effects of Different Dietary and Glycogen-Loaded Two-a-Day Training Approaches on Muscle Damage and Inflammatory Markers for Enhancing Metabolic Efficiency
by Serdar Şerare, Serkan Paçacı, Necip Arman, Ahmet Karadağ and Anıl Şahin
Metabolites 2026, 16(9), 674; https://doi.org/10.3390/metabo16090674 - 13 Sep 2026
Viewed by 450
Abstract
Background/Objective: Insufficient research has examined the muscle damage and inflammatory effects of training performed in a fasted state with reduced (low) glycogen reserves. Methods: This study aimed to investigate the acute effects of exercise sessions performed under fasting (FST) and liquid nutrient-supplemented postprandial [...] Read more.
Background/Objective: Insufficient research has examined the muscle damage and inflammatory effects of training performed in a fasted state with reduced (low) glycogen reserves. Methods: This study aimed to investigate the acute effects of exercise sessions performed under fasting (FST) and liquid nutrient-supplemented postprandial (PPD) conditions, as well as with full and reduced body glycogen stores, on muscle damage markers creatine kinase (CK) and lactate dehydrogenase (LDH), and the inflammatory marker interleukin-6 (IL-6). Eleven male amateur football players (mean age 19.91 ± 1.64 years) were included in the study. Participants performed a single 60 min aerobic endurance exercise session at 70% VO2max under the liquid nutrient-supplemented PPD condition, and two 60 min sessions with a 60 min recovery interval under 10–12 h FST conditions. Data were analyzed using paired samples t-test, ANOVA, Wilcoxon, and Friedman tests, depending on parametric and nonparametric assumptions. Results: In pre-exercise (PRE-FE) measurements, no significant differences were observed between the FST and PPD conditions for GLU, CK, LDH, and IL-6 levels. In postexercise (POST-FE) measurements, GLU levels were significantly higher in the PPD condition than in the FST condition (p < 0.05), whereas LA, CK, LDH, and IL-6 levels did not differ significantly between the two conditions. In the FST condition, following the second exercise session performed with default reduced glycogen availability (POST-SE), CK levels significantly increased from 279.36 ± 16.7 U/L to 335.63 ± 20.3 U/L, LDH levels from 178.72 ± 38.1 U/L to 208.09 ± 50.7 U/L, and IL-6 levels from 2.60 ± 2.4 pg/mL to 8.69 ± 5.8 pg/mL (p < 0.05). In the PPD condition, no significant changes were observed in any of the parameters following a single exercise session (p > 0.05). Conclusions: The two-a-day training approach performed with default reduced glycogen availability may increase muscle damage and inflammatory responses. These findings are considered as an inference that low-glycogen training should not be implemented during the pre-competition period because of the risk of inducing muscle damage. Full article
(This article belongs to the Special Issue Precision Exercise, Metabolic Health and Personalized Performance)
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25 pages, 1896 KB  
Article
Clinical Value of an LDH–CA125–NLR Panel for Diagnosis, Platinum Resistance, and Prognostic Assessment in Epithelial Ovarian Cancer
by Shuiqing Xu, Jinzhen Guo, Ziyi Zhao, Yan Zhai, Yingying Liu and Hua Li
Curr. Oncol. 2026, 33(9), 551; https://doi.org/10.3390/curroncol33090551 - 10 Sep 2026
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Abstract
(1) Background/Objective: Routine blood tests may provide useful information at different stages of epithelial ovarian cancer (EOC) management. This study evaluated continuous lactate dehydrogenase (LDH), carbohydrate antigen 125 (CA125), and neutrophil-to-lymphocyte ratio (NLR) values for diagnostic discrimination in epithelial ovarian cancer (EOC) and, [...] Read more.
(1) Background/Objective: Routine blood tests may provide useful information at different stages of epithelial ovarian cancer (EOC) management. This study evaluated continuous lactate dehydrogenase (LDH), carbohydrate antigen 125 (CA125), and neutrophil-to-lymphocyte ratio (NLR) values for diagnostic discrimination in epithelial ovarian cancer (EOC) and, separately, triple-positive status in relation to platinum resistance and survival. (2) Methods: This retrospective study included 238 patients with EOC and 238 individually matched patients with benign ovarian lesions. Continuous biomarkers were entered into logistic regression models for diagnosis. Triple-positive status was defined as LDH > 195.5 U/L, CA125 > 35.37 U/mL, and NLR > 2.63. Logistic regression was used for platinum resistance and Cox regression for progression-free survival (PFS) and overall survival (OS). Bootstrap internal validation was performed for the diagnostic models and PFS nomogram. (3) Results: The continuous LDH + CA125 + NLR model yielded an AUC of 0.873, with 75.97% sensitivity and 88.66% specificity; AUCs were 0.751 in early-stage and 0.958 in advanced-stage EOC. Adding NLR to LDH + CA125 did not significantly improve the AUC overall or within stage groups. Triple-positive status was associated with platinum resistance (adjusted OR = 3.488, 95% CI 1.504–8.087; p = 0.004), shorter PFS (adjusted HR = 3.109, 95% CI 1.772–5.456; p < 0.001), and shorter OS in advanced-stage EOC (adjusted HR = 3.538, 95% CI 1.385–9.038; p = 0.008). The PFS nomogram had a bootstrap-corrected C-index of 0.7521. (4) Conclusions: The continuous three-marker model showed diagnostic discrimination in this selected surgical cohort, while triple-positive status was associated with platinum resistance and adverse survival outcomes. External validation is needed. Full article
(This article belongs to the Section Gynecologic Oncology)
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24 pages, 10013 KB  
Article
Sentinel-2 Forel–Ule Index as a Proxy for Ecological Status in Reservoirs: A Case Study in Southern Portugal
by Mariana Campista Chagas, Ana Paula Falcão and Rodrigo Proença de Oliveira
Remote Sens. 2026, 18(18), 3109; https://doi.org/10.3390/rs18183109 - 10 Sep 2026
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Abstract
Water color is an important optical proxy for trophic status and water quality, but its integration into regulatory assessment frameworks is still limited. This study assesses the potential of the Forel–Ule Index (FUI) derived from Sentinel-2 as a proxy indicator to support the [...] Read more.
Water color is an important optical proxy for trophic status and water quality, but its integration into regulatory assessment frameworks is still limited. This study assesses the potential of the Forel–Ule Index (FUI) derived from Sentinel-2 as a proxy indicator to support the assessment of the ecological status of reservoirs under the European Union’s Water Framework Directive (WFD). Seventeen reservoirs located in semi-arid Mediterranean climate agricultural basins in southern Portugal (Sorraia, Sado, and Guadiana) were analyed, combining 4316 FUI observations (2017–2024) with in situ water quality data and official WFD ecological status classifications. The results showed that the values on the FUI scale (which ranges from 1 to 21) fell, for the most part, between 12 and 18 and with marked spatial and seasonal contrasts, particularly between more transparent reservoirs and persistently turbid ones, probably eutrophicated reservoirs. Principal component analysis showed that the first component (PC1, 39.5% of variance) represents a trophic gradient dominated by turbidity, chemical oxygen demand and chlorophyll-a, and is positively, albeit moderately, correlated with FUI (Spearman’s ρ = 0.439, p < 0.001), while the second component, dominated by nitrogen, showed no significant association. To make the Water Framework Directive (WFD) regulations compatible with the structure of the available dataset, ecological status was dichotomized into “Satisfactory” and “Deterioration”. Binary logistic regression showed that increasing FUI values were significantly associated with a lower probability of classification as “Satisfactory” (β = −0.682, p = 0.0137; odds ratio = 0.51, 95% CI: 0.29–0.87). The model performance was moderate (balanced accuracy = 0.682; AUC = 0.754), with better identification of “Deterioration” conditions than “Satisfactory” conditions. The Mann–Whitney U test confirmed that mean FUI values differed significantly between the two ecological status groups (U = 65, p = 0.0166), with lower values associated with reservoirs meeting the “Good” threshold. Overall, FUI proved to be a low-cost and temporally flexible screening and early-warning tool, particularly useful for identifying departures from favorable ecological conditions. However, the index is not a direct substitute for the official ecological classification and is best applied in combination with physicochemical and biological metrics when assessing changes in water quality over a shorter period of time. Full article
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18 pages, 4805 KB  
Article
Lactobacillus helveticus HY7804 Alleviates Ethanol-Induced Liver Injury and Modulates Oxidative Stress and Inflammatory Responses in a Chronic-Binge Ethanol-Fed Mouse Model
by Hyeonji Kim, Daehyeop Lee, Haeryn Jeong, Joo-Yun Kim, Jae-Jung Shim and Jae-Hwan Lee
Int. J. Mol. Sci. 2026, 27(18), 8058; https://doi.org/10.3390/ijms27188058 - 10 Sep 2026
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Abstract
Alcohol-associated liver disease (ALD) contributes substantially to the global burden of chronic liver disease, yet few effective pharmacological treatments are currently available. The hepatoprotective potential of Lactobacillus helveticus HY7804 was evaluated in ethanol-exposed HepG2 cells and in a modified chronic-binge ethanol-fed mouse model [...] Read more.
Alcohol-associated liver disease (ALD) contributes substantially to the global burden of chronic liver disease, yet few effective pharmacological treatments are currently available. The hepatoprotective potential of Lactobacillus helveticus HY7804 was evaluated in ethanol-exposed HepG2 cells and in a modified chronic-binge ethanol-fed mouse model adapted from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) paradigm. Ethanol-induced cytotoxicity in HepG2 cells was attenuated by HY7804, as demonstrated by the recovery of cell viability and the reduction in lactate dehydrogenase release. HY7804 also decreased ethanol-induced inflammatory cytokine production, including IL-6, TNF-α, IL-1β, and IL-8, and modulated apoptosis-related gene expression. In chronic-binge ethanol-fed mice, HY7804 reduced serum AST from 183.4 ± 34.1 to 129.4 ± 16.4 U/L (p < 0.01) and ALT from 67.5 ± 4.5 to 52.1 ± 4.7 U/L (p < 0.05). Hepatic lipid accumulation was also significantly reduced by HY7804 treatment compared with the EtOH group, as indicated by the decreased Oil Red O-positive area (p < 0.01). Hepatic MDA levels decreased from 46.01 ± 3.38 to 30.58 ± 6.38 nmol/mg tissue (p < 0.01). In addition, HY7804 modulated hepatic inflammatory cytokine profiles, antioxidant-related responses, and the Bax/Bcl-2 expression ratio. These findings suggest that HY7804 mitigates ethanol-induced hepatic injury, with associated changes in inflammatory responses, antioxidant-related markers, lipid peroxidation, and apoptosis-related gene expression. Full article
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