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17 pages, 2743 KB  
Article
Effects of Alkaline Mineral Complex Water Supplementation in the Diet on the Oxidative Stress, Immunity and Health of Lactating Cows
by Zhanshan Yang, Yang Zou, Erdan Wang and Shengli Li
Animals 2026, 16(18), 2915; https://doi.org/10.3390/ani16182915 - 16 Sep 2026
Viewed by 145
Abstract
Mid-lactation represents a critical production phase for high-yield dairy cows, where nutrient imbalance can compromise animal health and farm profitability. This study investigated the effects of dietary alkaline mineral complex (AMC)–water supplementation on milk yield, blood biochemistry, oxidative stress, immunity, hormone secretion and [...] Read more.
Mid-lactation represents a critical production phase for high-yield dairy cows, where nutrient imbalance can compromise animal health and farm profitability. This study investigated the effects of dietary alkaline mineral complex (AMC)–water supplementation on milk yield, blood biochemistry, oxidative stress, immunity, hormone secretion and ion status in mid-lactation dairy cows. A total of 120 high-yield mid-lactation Holstein cows were stratified into three milk yield subgroups (EHYG, HYG, MHYG) based on pre-experimental milk yield records. Within each yield stratum, 20 cows were randomly assigned to either the control group or the AMC-supplemented group, resulting in three control subgroups and three AMC-supplemented subgroups (n = 20 per subgroup). Controls received a basal diet, while cows in experimental groups received the basal diet supplemented with diluted AMC concentrate solution (1:4 concentrate to water, v/v) for 90 d. Blood samples were collected on days 0, 15, 30, 45, 60 and 90, and milk samples were obtained on days 0, 30, 60 and 90 to evaluate the production performance, stress and immune status. Dietary AMC supplementation reduced plasma NEFA (p < 0.01) and BHBA concentrations (p < 0.05). For hormone, oxidative-stress and immune indices, significant differences were detected only at discrete individual sampling time points, with no consistent overall treatment effects across the entire experimental period. No significant overall treatment effect of AMC supplementation was observed on the milk yield. These results provide preliminary reference data for alkaline mineral complex additive application in practical mid-lactation dairy production. Full article
(This article belongs to the Special Issue Novel Alternatives to Antibiotics for Sustainable Animal Production)
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21 pages, 697 KB  
Article
Effects of Mare Age and Number of Foalings on Body Morphometry, Udder Morphology, Milk Yield, and Milk Composition in Kushum Mares
by Maxat Toishimanov, Gulmira Bekova, Dastanbek Baimukanov, Dinara Begaliyeva, Anastasiya Yanina, Rakhim Kanat, Dias Daurov, Ainash Daurova, Zagipa Sapakhova, Gemingguli Muhatai, Zhaniya Assanbek, Alzhan Shamshidin, Indira Beishova and Malika Shamekova
Animals 2026, 16(18), 2864; https://doi.org/10.3390/ani16182864 - 11 Sep 2026
Viewed by 147
Abstract
Mare’s milk is recognized for its nutritional value, but information on the relationships of mare age and number of foalings with body conformation, udder morphology, milk yield, and milk composition in the indigenous Kushum breed remains limited. Forty-one clinically healthy lactating Kushum mares [...] Read more.
Mare’s milk is recognized for its nutritional value, but information on the relationships of mare age and number of foalings with body conformation, udder morphology, milk yield, and milk composition in the indigenous Kushum breed remains limited. Forty-one clinically healthy lactating Kushum mares were evaluated in June and classified by age (4–7, 8–11, and 12–16 years) and number of foalings (1–3, 4–7, and 8–11). Body traits were measured once; udder morphometry was available for 30 mares. Milk yield was recorded at 08:00, 10:00, 12:00, 14:00, and 16:00 h on two consecutive days. On Day 2, a 100-mL aliquot was collected after each milking, and the five aliquots were pooled into one 500-mL composite sample per mare; physicochemical composition was available for 40 mares. Age and number-of-foalings effects were evaluated in separate models. Continuous morphometric and physicochemical traits were analyzed by one-way ANOVA with Tukey-adjusted comparisons, with Benjamini–Hochberg false discovery rate (FDR) correction across trait families; two-day milk yield was additionally evaluated with a repeated-measures mixed model. After FDR correction, cannon bone circumference, body weight, udder length, and udder width differed among both age and number-of-foalings groups. Teat shape also differed among groups. The two-day mean daily milk yield did not differ by age (p = 0.483) or number of foalings (p = 0.195), although significant group-by-day interactions were detected. In pooled Day-2 milk, SNF, lactose, glucose, freezing point, acidity, lactic acid, density, and urea differed among both classification factors after FDR correction (q < 0.05), whereas fat, protein, total solids, galactose, citric acid, and casein did not. PCA explained 60.9% of the variance in body/udder traits plus mean milk yield and 68.8% of the variance in physicochemical composition. These findings indicate selective associations of age and number of foalings with Kushum mare phenotype and milk composition, while emphasizing the limitations of small udder subgroups and equal-volume pooled sampling. Full article
(This article belongs to the Section Equids)
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17 pages, 1169 KB  
Article
Enhancing Lactate Assimilation in Aspergillus oryzae by Small Amounts of Metabolic Co-Substrates and Low pH
by Hiroki Kikuta, Masamichi Muto, Naoko Tanaka, Tsuyoshi Tanaka and Junichi Mano
J. Fungi 2026, 12(9), 679; https://doi.org/10.3390/jof12090679 - 10 Sep 2026
Viewed by 423
Abstract
Lactate-rich byproducts and fermentation residues are generated during various food and fermentation processes, presenting opportunities for their conversion into value-added products through microbial bioprocesses. Aspergillus oryzae is a promising microbial host for such applications because of its ability to use diverse substrates and [...] Read more.
Lactate-rich byproducts and fermentation residues are generated during various food and fermentation processes, presenting opportunities for their conversion into value-added products through microbial bioprocesses. Aspergillus oryzae is a promising microbial host for such applications because of its ability to use diverse substrates and produce valuable products. However, the ability of A. oryzae to assimilate lactate and the factors limiting this process remain poorly understood despite its industrial importance. In this study, we investigated the transcriptional responses of A. oryzae during lactate assimilation and evaluated the culture conditions promoting this process. A. oryzae demonstrated only limited growth and lactate consumption when lactate was provided as its only carbon source in the synthetic minimal medium. Transcriptome analysis suggested possible metabolic constraints associated with carbon flux into the tricarboxylic acid (TCA) cycle, limiting lactate assimilation. To alleviate these constraints, the culture conditions were examined. Supplementation with small amounts of sugars, specific amino acids, and α-ketoglutarate promoted lactate assimilation. Moreover, low-pH conditions further improved lactate assimilation, reducing residual lactate concentrations to below the detection limit. These findings indicate that efficient lactate assimilation is promoted by small amounts of metabolic co-substrates, potentially through effects on central carbon metabolism, together with favorable low-pH conditions. Full article
(This article belongs to the Special Issue Fungi in Focus: Fungal Enzyme and Fungal Metabolism)
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30 pages, 48223 KB  
Article
DRG-LiteStar-YOLO: Reliability-Guided Pseudo-Depth Fusion for Dairy Goat Detection in Complex Barns
by Yongliang Zhang, Keyuan Wang, Yue Yang and Nan Geng
Animals 2026, 16(18), 2840; https://doi.org/10.3390/ani16182840 - 9 Sep 2026
Viewed by 205
Abstract
Reliable dairy goat detection in barns is challenging because uneven illumination, railings, and animal overlap weaken RGB boundaries. We developed DRG-LiteStar-YOLO, a lightweight RGB-camera-compatible detector that integrates monocular pseudo-depth with RGB features without requiring a dedicated depth sensor. DA3-Small was used to generate [...] Read more.
Reliable dairy goat detection in barns is challenging because uneven illumination, railings, and animal overlap weaken RGB boundaries. We developed DRG-LiteStar-YOLO, a lightweight RGB-camera-compatible detector that integrates monocular pseudo-depth with RGB features without requiring a dedicated depth sensor. DA3-Small was used to generate relative pseudo-depth maps, which were fused with RGB features through reliability-guided fusion and boundary-enhanced multi-scale aggregation. The dataset comprised 1521 images of 134 lactating Saanen goats and 13,985 annotated instances. On the held-out test set, DRG-LiteStar-YOLO achieved a precision of 0.961, a recall of 0.941, an mAP@0.5 of 0.978, and an mAP@0.5:0.95 of 0.735. Compared with RGB-only LiteStar-YOLO, the proposed method improved mAP@0.5 and mAP@0.5:0.95 by 1.6 and 3.8 percentage points, respectively. The five-seed cumulative ablation further showed that the full configuration achieved 0.734±0.002 mAP@0.5:0.95 compared with 0.697±0.004 for RGB-only LiteStar-YOLO. The detector contains 4.20 M parameters and 12.60 GFLOPs and achieves 86.2 FPS on an RTX 4090 with precomputed pseudo-depth maps. These results demonstrate that reliability-guided pseudo-depth fusion improves goat localization under complex barn conditions while retaining a compact detector design. DRG-LiteStar-YOLO provides an effective perception framework for RGB-camera-based dairy goat monitoring and supports future counting, tracking, and behavior-analysis applications. Full article
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15 pages, 644 KB  
Article
Biochemical Markers in Pleural Fluid for the Diagnosis of Tuberculous Pleural Effusion: A Retrospective Study
by Natalia Zaporojan, Ramona Hodișan, Claudiu Zaporojan, Andreea Atena Zaha, Andrei Nicolae Csep and Dana Carmen Zaha
Diseases 2026, 14(9), 327; https://doi.org/10.3390/diseases14090327 - 9 Sep 2026
Viewed by 233
Abstract
Background/Objectives: The rapid diagnosis of tuberculous pleural effusion (TPE) presents significant challenges for clinicians due to its paucibacillary nature. Routine biochemical markers may complement microbiological and molecular tests, especially in resource-limited settings. The objective of this study was to evaluate the diagnostic performance [...] Read more.
Background/Objectives: The rapid diagnosis of tuberculous pleural effusion (TPE) presents significant challenges for clinicians due to its paucibacillary nature. Routine biochemical markers may complement microbiological and molecular tests, especially in resource-limited settings. The objective of this study was to evaluate the diagnostic performance of pleural fluid adenosine deaminase (ADA), lactate dehydrogenase (LDH), total protein (TP), and the ADA/LDH and ADA/TP ratios for tuberculous pleural effusion, using Löwenstein–Jensen culture and Xpert MTB/RIF as microbiological reference standards Methods: We conducted a retrospective study (2016–2024) including 325 consecutive patients investigated for suspected TPE in a tertiary hospital. ADA, TP and LDH were measured, and additional ratio-based indices (ADA/TP, ADA/LDH) were calculated for 325 pleural fluid (PF) samples. Löwenstein–Jensen (LJ) culture (with MPT64 confirmation) and GeneXpert MTB/RIF (Xpert MTB/RIF) were used as separate microbiological reference standards. Sensitivity (Se), specificity (Sp), and areas under the ROC curve (AUC) were estimated, and optimal thresholds were determined using the Youden index. Results: Among 325 pleural fluid samples, 23 (7.1%) were culture-positive. Xpert MTB/RIF was performed in 73/325 patients (22.5%), with Mycobacterium tuberculosis detected in 19/73 (26.0%) tested samples. In PF, ADA provided the best performance against culture, with Se of 100%. Correlation analysis in PF showed a moderate positive association between TP and LDH (p < 0.0001). Conclusions: Among routine biochemical markers, PF ADA shows high NPV. Integrating these rapid, low-cost tests alongside LJ culture and Xpert MTB/RIF may streamline the diagnostic pathway for TPE. Full article
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26 pages, 10711 KB  
Article
A Flexible Wearable Multisensing Patch Integrating SWCNT-PtNPs Nanocomposites for Non-Invasive Clinical Biomarkers Monitoring in Sweat
by Lucian-Gabriel Zamfir, Petru Epure, Ioana Cătălina Gîfu, Iuliana Răut, Mariana Constantin, Cristina Firincă, Nicoleta-Olguța Corneli, Mihaela Doni and Ana-Maria Gurban
Polymers 2026, 18(17), 2150; https://doi.org/10.3390/polym18172150 - 2 Sep 2026
Viewed by 279
Abstract
The integration of enzyme-loaded polymeric matrices with carbon-based nanomaterials and metallic nanoparticles into wearable multisensing patches, coupled with miniaturized portable detection devices, enables real-time, highly sensitive, and simultaneous monitoring of key clinical biomarkers (e.g., glucose, lactate, and H2O2) in [...] Read more.
The integration of enzyme-loaded polymeric matrices with carbon-based nanomaterials and metallic nanoparticles into wearable multisensing patches, coupled with miniaturized portable detection devices, enables real-time, highly sensitive, and simultaneous monitoring of key clinical biomarkers (e.g., glucose, lactate, and H2O2) in clinical and point-of-care applications. Multiplex biosensors were fabricated by modifying screen-printed carbon paste electrodes (SPEs) with different composite nanomaterials based on carbon nanomaterials such as multi-walled carbon nanotubes (MWCNTs), single-walled carbon nanotubes (SWCNTs), or fullerenol (FL), the redox mediator Prussian Blue, and platinum nanoparticles (PtNPs). Chitosan and sol–gel polymer matrices were used to immobilize the enzymes glucose oxidase (GOx) and lactate oxidase (LOx), thus ensuring not only increased sensitivity and operational stability, but also high specificity for biomarker detection (glucose and lactate). Among the nanomaterials used for the development of multiplex biosensors, the SWCNT-PtNP composite was highlighted by electrochemical studies as having a significantly superior electrocatalytic activity toward the reduction of H2O2. This reaction occurs at a low applied potential of only −0.2 V vs. Ag/AgCl, achieving a specific sensitivity of 224.6 mA·M−1·cm−2, over a concentration range of 0.07 to 28.26 mM, and a detection limit of 3.2 μM. When functionalized with enzymes, SWCNT-PtNP-based biosensors exhibit improved conductivity, allowing the detection of glucose and lactate at a potential of −0.05 V vs. Ag/AgCl. The specific sensitivities obtained are 20.25 mA·M−1·cm−2 for glucose and 94.76 mA·M−1·cm−2 for lactate, and the corresponding detection limits are 23.6 μM and 5.0 μM, respectively. Finally, a wearable patch integrating the multiplex (bio)sensor with a portable potentiostat enabled simultaneous, sensitive, and selective detection of glucose, lactate, and H2O2 in sweat samples. Full article
(This article belongs to the Topic Advanced Materials for Flexible and Wearable Electronics)
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31 pages, 11931 KB  
Article
Beyond Body Weight: Maternal Propolis Selectively Modulates Metabolic and Hepatic Outcomes in Male and Female Rat Offspring Exposed to a Maternal Cafeteria Diet
by Kadriye Elif İmre and Aslı Akyol
Nutrients 2026, 18(17), 2881; https://doi.org/10.3390/nu18172881 - 2 Sep 2026
Viewed by 302
Abstract
Background/Objectives: Maternal obesogenic diets may produce persistent developmental alterations in offspring, with response patterns that may differ between males and females. We investigated whether propolis supplementation from preconception through lactation modified metabolic and hepatic outcomes in offspring exposed to a maternal cafeteria [...] Read more.
Background/Objectives: Maternal obesogenic diets may produce persistent developmental alterations in offspring, with response patterns that may differ between males and females. We investigated whether propolis supplementation from preconception through lactation modified metabolic and hepatic outcomes in offspring exposed to a maternal cafeteria diet. Methods: Thirty-two Wistar rat dams received a control diet (CON), cafeteria diet (CAF), or either diet with propolis in drinking water (CONP and CAFP; target exposure, 200 mg/kg/day). One male and one female per litter (n = 8/sex/group) received standard chow after weaning. This design isolated maternal exposure because offspring received no propolis after weaning. At 18 weeks, metabolic and inflammatory biomarkers, liver histopathology, and hepatic lipid-metabolism gene expression were evaluated using groupwise tests and two-way ANOVA. Results: Final body weights were comparable across groups. In males, maternal diet affected glucose (p = 0.034) and HOMA-IR (p = 0.023), with a diet × propolis interaction for glucose (p = 0.042). CAF males had higher TNF-α than CAFP and CONP males. In females, diet × propolis interactions were detected for insulin, total cholesterol, triglycerides, and leptin (all p ≤ 0.049); CAF females had higher triglycerides than CON and CAFP females. Hydropic degeneration was greater in CAF dams than all other groups and in CAF than CONP male offspring; female histopathology did not differ. Male hepatic gene expression did not differ among groups, whereas female PPAR-β and FADS2 showed propolis main effects (p = 0.046 and p = 0.009, respectively). Conclusions: Maternal cafeteria-diet exposure was associated with persistent metabolic and hepatic alterations despite comparable offspring body weights, with different response patterns observed in the separate male and female analyses. Maternal propolis supplementation selectively modified some inflammatory, lipid-related, and histopathological outcomes; however, these effects were heterogeneous and did not consistently normalize the cafeteria-associated phenotype. Overall, the findings support partial, endpoint-specific, and context-dependent modulation rather than uniform metabolic or hepatic protection. Full article
(This article belongs to the Section Nutrition and Metabolism)
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13 pages, 247 KB  
Article
Exercise-Induced Acid–Base, Electrolyte, and Metabolic Responses in Colombian Creole Horses Across Different Gait Modalities
by Angélica María Zuluaga-Cabrera, José Eduardo Escobar-Riomalo, María Fernanda Giraldo-Arboleda, Juan Manuel Morales-Castañeda, Guilherme Barbosa da Costa, Iván Darío Martinez, Yasser Y. Lenis and María Patricia Arias-Gutiérrez
Animals 2026, 16(17), 2738; https://doi.org/10.3390/ani16172738 - 2 Sep 2026
Viewed by 494
Abstract
Exercise physiology in Colombian Creole Horses remains poorly characterized despite the breed’s extensive use in athletic activities. The objective of this study was to evaluate exercise-induced changes in blood biochemical and gas parameters and to determine whether these responses differed according to sex, [...] Read more.
Exercise physiology in Colombian Creole Horses remains poorly characterized despite the breed’s extensive use in athletic activities. The objective of this study was to evaluate exercise-induced changes in blood biochemical and gas parameters and to determine whether these responses differed according to sex, geographic origin, or gait modality. An analytical observational study with repeated measures was conducted in 76 athletic CCHs. Blood samples were obtained from the jugular vein at rest and immediately after exercise to measure acid–base indicators (pH, carbon dioxide pressure, bicarbonate), electrolytes (sodium, potassium, calcium, chloride), and metabolic variables (glucose, lactate, creatinine). Within-subject comparisons were performed to quantify exercise-induced changes, and subgroup analyses were conducted by sex, geographic region, and gait modality. Exercise resulted in physiologically consistent responses, including a mild reduction in pH (−0.01), decreases in carbon dioxide pressure (−2.39 mmHg) and bicarbonate (−1.7 mmol/L), and a moderate increase in lactate (+2.96 mmol/L), indicating exercise-associated metabolic acidosis and anaerobic metabolism. Glucose and creatinine also increased modestly, while electrolyte concentrations remained relatively stable. No meaningful differences were detected between sexes or geographic regions. As expected, gait modality significantly influenced acid–base responses, with horses performing trocha exhibiting greater reductions in carbon dioxide pressure and bicarbonate. These findings indicate that gait type modulates the magnitude of exercise-induced acid–base responses in Colombian Creole Horses. Full article
15 pages, 3038 KB  
Article
A Logistic Regression Model Integrating Flow Cytometry−Derived Immune Cell Profiles and Hematological Parameters for Preoperative Prediction of Peritoneal Metastasis in Gastric Cancer
by Ruihu Zhao, Yuming Ju, Zhichao Yu, Yingwei Xue and Hongjiang Song
Cancers 2026, 18(17), 2813; https://doi.org/10.3390/cancers18172813 - 30 Aug 2026
Viewed by 336
Abstract
Background: Peritoneal metastasis (PM) is a lethal and often occult event in advanced gastric cancer (GC), and its preoperative detection remains difficult. The role of peripheral NK and NKT−like cells in predicting PM has not been well defined. Methods: We retrospectively analyzed 433 [...] Read more.
Background: Peritoneal metastasis (PM) is a lethal and often occult event in advanced gastric cancer (GC), and its preoperative detection remains difficult. The role of peripheral NK and NKT−like cells in predicting PM has not been well defined. Methods: We retrospectively analyzed 433 patients who underwent surgery for GC from 2016 to 2020. Patients were stratified by PM status and randomly assigned to training and held−out internal validation cohorts. Flow cytometry−derived lymphocyte subset percentages were treated as compositional data, and NK and NKT−like cell variables were entered into the model after log−ratio transformation. Candidate variables were selected using LASSO logistic regression in the training cohort and further assessed by multivariable logistic regression. Model performance was evaluated using AUROC, AUPRC, and confusion matrices in the validation cohort. Nomogram and SHAP analyses were used for model interpretation. Results: Seven predictors were retained in the final model: log−ratio−transformed NKT−like cells, direct bilirubin, prealbumin, lymphocyte count, lactate dehydrogenase, CA125, and log−ratio−transformed NK cells. The model achieved an AUROC of 0.879 (95% CI: 0.805–0.936) and an AUPRC of 0.698 (95% CI: 0.524–0.848) in the validation cohort. At the conventional threshold of 0.50, the model achieved an accuracy of 0.915, sensitivity of 0.821, specificity of 0.941, PPV of 0.793, and NPV of 0.950. At the Youden−optimal threshold of 0.101, sensitivity, specificity, accuracy, PPV, and NPV were 1.000, 0.892, 0.915, 0.718, and 1.000, respectively. Conclusions: A preoperative model integrating log−ratio−transformed NK/NKT−like cell variables and routine hematological parameters showed good ability to identify PM in GC and may help select patients for diagnostic laparoscopy or closer preoperative evaluation. Full article
(This article belongs to the Topic Biomarker Development and Application, 2nd Edition)
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39 pages, 3525 KB  
Review
From Traditional Remedy to Evidence-Based Phytotherapeutic Agent: Hedera helix L. in Respiratory Medicine
by Agata Maria Pawłowska
Plants 2026, 15(17), 2610; https://doi.org/10.3390/plants15172610 - 27 Aug 2026
Viewed by 465
Abstract
Hedera helix L. leaf extracts are regulated expectorants for productive cough, yet their evidence is dispersed across pharmaceutical quality, nonclinical pharmacology, disposition, toxicology, clinical pharmacology, efficacy, safety, and regulatory assessment. This review integrates those domains in a single study-level account and explicitly distinguishes [...] Read more.
Hedera helix L. leaf extracts are regulated expectorants for productive cough, yet their evidence is dispersed across pharmaceutical quality, nonclinical pharmacology, disposition, toxicology, clinical pharmacology, efficacy, safety, and regulatory assessment. This review integrates those domains in a single study-level account and explicitly distinguishes isolated constituents, incompletely specified extracts, defined monograph preparations, proprietary extracts, and combination products. Hederacoside C is the pharmacopoeial marker, while α-hederin is the constituent most extensively examined in β2-adrenergic receptor models. Cell studies documented reduced agonist-induced receptor internalisation, greater ligand binding and cAMP responsiveness, and altered GRK2/β-arrestin signalling. Isolated tissue and animal studies reported antispasmodic, anti-inflammatory, antitussive, and tracheobronchial secretory effects. Rat studies showed low, matrix-dependent oral exposure to hederacoside C and α-hederin. Small exploratory human studies detected no or only trace α-hederin and did not permit conventional pharmacokinetic analysis. Clinical evidence includes placebo-controlled adult trials, active comparator studies, paediatric investigations, postmarketing cohorts, systematic reviews, and pharmacovigilance reports. Controlled adult trials of EA 575 reported greater short-term improvement in cough or Bronchitis Severity Score than placebo; paediatric efficacy evidence is dominated by observational studies and small airway function trials. Short-term tolerability was generally favourable, with gastrointestinal and hypersensitivity reactions as the principal recognised adverse effects. The European Union monograph recognises specified extracts for productive cough, contraindicates use below two years, and does not recommend use during pregnancy or lactation. The distinctive contribution of this review is the complete quality-to-clinic evidence map, including dose, model, endpoint, study design, extract identity, and unresolved evidence domain for each major dataset. Full article
(This article belongs to the Special Issue Advances in Medicinal Plant Phytochemistry and Phytotherapy)
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19 pages, 1655 KB  
Article
Live-Cell Optical Redox Imaging Reveals Metabolic Heterogeneity and Context-Dependent Responses to Metabolic Perturbation in TNBC Cells
by He N. Xu, Jack Kollmar, Allison Podsednik, Mihiar Wannousse, Alexander Shestov, Roddy S. O’Connor, Joseph A. Baur, Julia Tchou, Rong Zhou and Lin Z. Li
Metabolites 2026, 16(9), 613; https://doi.org/10.3390/metabo16090613 - 27 Aug 2026
Viewed by 370
Abstract
Background/Objectives: Triple-negative breast cancer (TNBC) exhibits substantial metabolic heterogeneity and plasticity, contributing to variable therapeutic responses. We investigated whether optical redox imaging (ORI) could characterize metabolic phenotypes, monitor responses to metabolic perturbation, and relate these responses to functional outcomes in TNBC cells. Methods: [...] Read more.
Background/Objectives: Triple-negative breast cancer (TNBC) exhibits substantial metabolic heterogeneity and plasticity, contributing to variable therapeutic responses. We investigated whether optical redox imaging (ORI) could characterize metabolic phenotypes, monitor responses to metabolic perturbation, and relate these responses to functional outcomes in TNBC cells. Methods: Four TNBC cell lines were treated with the lactate dehydrogenase A inhibitor FX11 or the glutaminase inhibitor CB-839, alone or in combination with paclitaxel. Intensity-based label-free ORI was performed and followed by imaging of fluorescent probes to assess mitochondrial membrane potential (MMP), re-active oxygen species (ROS), and cell number in the same dishes. Seahorse assays were used to evaluate mitochondrial respiration and glycolytic flux. Results: TNBC cell lines exhibited distinct basal redox phenotypes and differential responses to acute glycolytic and glutaminolytic perturbation. HCC1806 cells showed the strongest acute ORI responses to both FX11 and CB-839. Acute FX11 treatment induced a rapid reductive shift accompanied by ROS accumulation and loss of MMP, whereas CB-839 produced a more modest early reductive response without detectable ROS accumulation or MMP loss. Prolonged treatment revealed distinct temporal redox trajectories in HCC1806 cells: FX11-treated cells evolved from an acute reductive response toward a more oxidized state, while CB-839-treated cells transitioned from an early reductive shift to a sustained oxidized redox state accompanied by marked reductions in OCR and ECAR. Functionally, in two representative models (HCC1806 and MDA-MB-231), CB-839 reduced cell numbers and enhanced the anti-proliferative effect of paclitaxel, whereas FX11 had no significant effect on cell number despite inducing pronounced acute redox perturbations. Conclusions: Integrating ORI with metabolic flux assays and imaging-based functional measurements enables characterization of multiple dimensions of metabolic behavior, including basal phenotype, pathway-specific responsiveness, temporal redox responses, and treatment-associated outcomes. These findings support intensity-based wide-field ORI as a practical and accessible tool for probing metabolic heterogeneity and characterizing context-dependent metabolic responses in TNBC cells. Full article
(This article belongs to the Special Issue Optical Assessment of Metabolism—2nd Edition)
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13 pages, 831 KB  
Article
Impact of MOOC-Based CME on General Practitioners’ Knowledge of Early-Life Nutrition
by Yoga Devaera, Yulia Ariani, Titis Prawitasari, Diantha Soemantri, Desak Gede Budi Krisnamurti and Rizki Marfira
Int. Med. Educ. 2026, 5(3), 91; https://doi.org/10.3390/ime5030091 - 26 Aug 2026
Viewed by 187
Abstract
General practitioners (GPs) are at the forefront of stunting interventions, but only a few studies have examined their understanding of growth monitoring. Therefore, this study aims to assess the effectiveness of massive open online course (MOOC)-based Continuing Medical Education (CME) programs to increase [...] Read more.
General practitioners (GPs) are at the forefront of stunting interventions, but only a few studies have examined their understanding of growth monitoring. Therefore, this study aims to assess the effectiveness of massive open online course (MOOC)-based Continuing Medical Education (CME) programs to increase GPs’ knowledge of nutrition and early detection of growth abnormalities. The study procedures were carried out using a pre- and post-cohort approach involving 121 GPs, mostly working in primary care in Indonesia. The pre- and post-test scores were observed before and after the 12-week MOOC intervention, and the participants were asked for feedback. There were 190 verified participants; the attrition rate was 27.4% (n = 52), and there were six participants with incomplete data, leaving 121 participants as the final sample. The results showed that post-test scores significantly increased after intervention in all domains. These domains included early-life nutrition (7.00 to 9.00), breastfeeding and lactation management (5.56 to 7.78), and feeding problems (7.33 to 8.00) (p < 0.001). Participants reported high satisfaction and preferred a combination of synchronous and asynchronous learning. The feedback suggested improving parental education techniques, specifically in low-socioeconomic settings, and strengthening collaboration between GPs and nutritionists in managing feeding problems. Full article
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24 pages, 20236 KB  
Article
GPR81 Regulates MCT1 Membrane Translocation Through a PKA-Dependent Signaling Pathway in Rat Podocytes
by Klaudia Grochowalska, Maria Szrejder, Irena Audzeyenka and Agnieszka Piwkowska
Int. J. Mol. Sci. 2026, 27(17), 7563; https://doi.org/10.3390/ijms27177563 - 24 Aug 2026
Viewed by 325
Abstract
Podocytes and their foot processes form a functional layer of the glomerular filtration barrier. Due to their unique morphology and function, podocytes employ distinct nutrient pathways to maintain the bioenergetic balance, with lactate being one of several available energy substrates. Enhanced lactate intake [...] Read more.
Podocytes and their foot processes form a functional layer of the glomerular filtration barrier. Due to their unique morphology and function, podocytes employ distinct nutrient pathways to maintain the bioenergetic balance, with lactate being one of several available energy substrates. Enhanced lactate intake modulates the redox state of the cell by increasing mitochondrial respiration and reactive oxygen species production. Monocarboxylate transporter 1 (MCT1) is the primary lactate transporter, and alterations in its surface expression may contribute to the regulation of lactate uptake in podocytes. Beyond its metabolic role, lactate also acts as a crucial signaling molecule by binding to G-protein-coupled receptor 81 (GPR81), mediating a wide range of physiological effects through the inhibition of protein kinase A (PKA). The present study investigated novel regulatory mechanisms of MCT1 internalization, which depend on GPR81 signaling and PKA activity in primary rat podocytes, through the biotinylation assay. Surprisingly, both PKA inhibition (with H89 and PKI 14–22) and activation (with 8-bromo-cAMP and H2O2) increased MCT1 internalization. GPR81 was also found to regulate MCT1 membrane trafficking, likely through the modulation of PKA activity but also potentially through PKA-independent mechanism. Additionally, general dynamic changes in endocytic activity were detected under the present conditions with pHrodo-dextran fluorescence analysis. These results suggest that the modulation of PKA activity and GPR81 signaling may regulate lactate transport via MCT1, thereby ensuring its proper metabolic function in podocytes. Full article
(This article belongs to the Section Biochemistry)
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20 pages, 8769 KB  
Article
Association of Hypoxia-Induced Lactate Accumulation with AARS2 Expression, PDHA1/CPT2 Lactylation, and Energy Metabolism in Yak Skeletal Muscle Cells
by Tianshuai Li, Zhengbo Li, Jialin Wang, Miaoran Li, Kangfei An, Qixin Wang, Guoxiu Li, Lingxia Li, Jianshu Lv, Xiangdong Ye and Xiaodong Ling
Cells 2026, 15(17), 1515; https://doi.org/10.3390/cells15171515 - 23 Aug 2026
Viewed by 270
Abstract
Yaks (Bos grunniens) are a typical species inhabiting high-altitude environments; however, their molecular responses to hypoxic conditions remain incompletely understood. This study aimed to investigate associations among alanyl-transfer RNA synthetase 2 (AARS2) expression, lactylation of pyruvate dehydrogenase E1 alpha 1 (PDHA1) [...] Read more.
Yaks (Bos grunniens) are a typical species inhabiting high-altitude environments; however, their molecular responses to hypoxic conditions remain incompletely understood. This study aimed to investigate associations among alanyl-transfer RNA synthetase 2 (AARS2) expression, lactylation of pyruvate dehydrogenase E1 alpha 1 (PDHA1) and carnitine palmitoyltransferase 2 (CPT2), and energy metabolism under hypoxic conditions in yaks. Oxygen-sensitive tissues (skeletal muscle, cardiac muscle, and lungs) collected from yaks at different altitudes, along with primary yak skeletal muscle cells, were analyzed using RT-qPCR, Western blotting, immunofluorescence (IF), and co-immunoprecipitation (co-IP). In tissues from the three altitude groups, AARS2 expression was higher in the higher-altitude groups (p < 0.05), whereas PDHA1 and CPT2 expression was lower (p < 0.01). Overall protein lactylation levels were also higher in tissues from the higher-altitude groups. Under hypoxic conditions, lactate levels and AARS2 expression increased in skeletal muscle cells, accompanied by increased activities of key glycolytic enzymes and decreased activities of enzymes related to mitochondrial oxidative phosphorylation. Galloflavin treatment reduced lactate levels and partially attenuated these metabolic changes. Endogenous co-IP detected lactylation of both PDHA1 and CPT2. Following siRNA-mediated knockdown of AARS2, the protein abundance of PDHA1 and CPT2 increased. Taken together, these findings support an association between hypoxia-induced lactate accumulation, increased AARS2 expression, PDHA1/CPT2 lactylation, and a shift in cellular energy metabolism toward glycolysis. This study provides a theoretical basis for further understanding hypoxia-related metabolic remodeling in yaks. Full article
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20 pages, 1064 KB  
Review
Spinal Cord Ischemia After Thoracoabdominal Aortic Aneurysm Repair: Pathophysiology, Detection, and Management
by Janak Patel, Stephanie Liang, Mirza Bulic, May Kim-Tenser, Tatsuhiro Fuji, Sukgu Han, Benjamin Emanuel and Fawaz Philip Tarzi
Neurol. Int. 2026, 18(8), 156; https://doi.org/10.3390/neurolint18080156 - 20 Aug 2026
Viewed by 525
Abstract
Thoracoabdominal aortic aneurysm (TAAA) is a complex vascular disorder involving both thoracic and abdominal segments of the aorta and remains associated with substantial morbidity and mortality. One of the most serious complications after thoracoabdominal aortic aneurysm (TAAA) repair is spinal cord ischemia (SCI), [...] Read more.
Thoracoabdominal aortic aneurysm (TAAA) is a complex vascular disorder involving both thoracic and abdominal segments of the aorta and remains associated with substantial morbidity and mortality. One of the most serious complications after thoracoabdominal aortic aneurysm (TAAA) repair is spinal cord ischemia (SCI), which may progress to spinal cord infarction and result in irreversible neurologic deficits including paraplegia, neurogenic bladder dysfunction, and bowel dysfunction. The incidence of SCI after TAAA repair varies with the extent of aneurysmal involvement, operative duration, and patient comorbidities. The primary pathophysiologic mechanism involves interruption of radiculomedullary arterial flow, compounded by systemic hypotension and limited collateral circulation. Because SCI profoundly affects functional recovery and long-term quality of life, prevention and early recognition are central to perioperative management. Established neuroprotective strategies emphasize maintenance of spinal cord perfusion through meticulous hemodynamic optimization, cerebrospinal fluid (CSF) drainage, and temperature modulation. Intraoperative neuromonitoring using motor and somatosensory-evoked potential facilitates early detection, while newer modalities such as near-infrared spectroscopy and CSF lactate monitoring may offer additional insight. When SCI occurs despite prophylaxis, rapid initiation of rescue measures including CSF drainage, hemodynamic augmentation, and other discussed treatments may improve neurologic outcomes. Long-term care focuses on rehabilitation, symptom management, and psychological support. Therefore, this review aims to consolidate medical evidence to improve the prevention, detection, and treatment of spinal cord infarction associated with thoracoabdominal aortic aneurysm repair. Full article
(This article belongs to the Special Issue Spinal Cord Injury: Emerging Therapeutics and Neurorehabilitation)
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