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33 pages, 1756 KB  
Article
Improving the Efficiency of Computer Networks Based on the Use of Seamless Wi-Fi Technology—The Use of Artificial Intelligence for Sustainable Agriculture
by Anita Konieczna, Roman Padyuka, Anatoliy Tryhuba, Pavlo Lub, Vadym Ptashnyk, Kinga Borek, Anna Rygało-Galewska, Barbara Dybek, Dorota Anders, Kamila Klimek, Adam Koniuszy and Grzegorz Wałowski
Appl. Sci. 2026, 16(16), 7916; https://doi.org/10.3390/app16167916 (registering DOI) - 8 Aug 2026
Abstract
Improving the performance of computer networks using seamless Wi-Fi can be achieved by implementing a number of strategies and technologies. Strategies include, first of all, the optimal location of routers and access points, the use of a multi-band network or routers supporting different [...] Read more.
Improving the performance of computer networks using seamless Wi-Fi can be achieved by implementing a number of strategies and technologies. Strategies include, first of all, the optimal location of routers and access points, the use of a multi-band network or routers supporting different bands. Routers with support for beamforming technology, which directs the Wi-Fi signal directly to connected devices, allow you to improve the signal quality and data transfer speed. Increasing the performance of Wi-Fi computer networks is also provided by the use of network monitoring and management software, which allows you to monitor its performance and respond to possible problems in the network infrastructure. This is an important task, because it determines the quality and convenience of access to network resources. First of all, it allows you to achieve a high data transfer rate, which is especially important in conditions of high traffic necessary for demanding applications. Seamless Wi-Fi technologies also promote increased mobility and flexibility of users, allowing them to connect to the network in any place with a good signal without having to use wired connections. Network management becomes more efficient with automatic switching between access points and increased fault tolerance in the face of changing traffic usage scales. Quantitative results: Implementation of the Wi-Fi roaming mechanism using the IEEE 802.11 specification; Wi-Fi performance measurements obtained for various IEEE 802.11n HT20 and IEEE 802.11a client ratios; the original test environment included 50 laptops and netbooks from various manufacturers, equipped with various operating systems and wireless network adapters; seamless Wi-Fi technologies based on IEEE 802.11k, IEEE 802.11v, and IEEE 802.11r improve communication continuity during device mobility and support real-time AI-based decision making; Wi-Fi based on local communication standards (WLAN-Wireless Local Area Network). It allows data transmission speeds from 1 Mb∙s1 to 6.75 Gb∙s1. Indoors, the Wi-Fi range is 20 m, and outdoors 100 m; WiMax (Worldwide Interoperability for Microwave Access) is a built-in set of wireless broadband standards that provide a constant data rate of 1 Gb∙s1 and 100 Mb∙s1 in a cellular network; LR-WPANs (Low-Rate Wireless Personal Area Networks) are standards that are the basis for higher communication protocols, ZigBee. They offer data rates ranging from 40 kb to 250 kb∙s1. In devices with limited resources, these standards operate at 2.4 GHz at higher transmission speeds and 868/915 MHz at lower. The novelty in the article is the implementation of the Wi-Fi roaming mechanism, presentation of Wi-Fi scenarios, discussion of module generations, indication of integrated agriculture in terms of modern digitalization technologies, and characteristics of smart farming. Full article
22 pages, 4922 KB  
Article
Integrating Metabolomics and Transcriptomics Reveals the Multi-Target Mechanisms of Fermented Portulaca oleracea L. (Purslane) in Attenuating Acute Diarrhea
by Rui Chen, Chunnan Yan, Xiyu Li, Xiaona Pang, Junhua Jin, Hongxing Zhang and Yuanhong Xie
Nutrients 2026, 18(16), 2595; https://doi.org/10.3390/nu18162595 - 7 Aug 2026
Abstract
Background: Current understanding of the biotransformation of bioactive compounds in Portulaca oleracea through probiotic fermentation remains limited, and the anti-diarrheal mechanisms of the resulting fermented products have yet to be fully elucidated. Methods: In this exploratory study, we employed untargeted metabolomics together with [...] Read more.
Background: Current understanding of the biotransformation of bioactive compounds in Portulaca oleracea through probiotic fermentation remains limited, and the anti-diarrheal mechanisms of the resulting fermented products have yet to be fully elucidated. Methods: In this exploratory study, we employed untargeted metabolomics together with a senna-induced acute diarrhea mouse model to investigate P. oleracea co-fermented with Lactiplantibacillus plantarum and Bacillus subtilis. Results: Metabolomic profiling identified 220 metabolites significantly altered by fermentation, predominantly comprising increased levels of lipids, phenylpropanoids, and polyketides. Compared with the unfermented P. oleracea control, fermented P. oleracea (FP) effectively reduced the diarrhea index, lowered serum levels of inflammatory cytokines (IL-1β, IL-6, TNF-α) and neurotransmitters (5-HT, substance P), and restored Na+/K+ balance as well as ileal histomorphology. Transcriptomic analysis and RT-qPCR validation further demonstrated that FP modulated the expression of genes involved in focal adhesion, PI3K-Akt, cGMP-PKG, and mineral absorption pathways. Conclusions: Fermented P. oleracea (FP) alleviates acute diarrhea through multi-target mechanisms. Notably, fermentation endows P. oleracea with markedly superior intestinal protective effects relative to the unfermented counterpart. These findings provide preliminary experimental evidence supporting the potential of fermented P. oleracea as a candidate for intestinal protective functional food research. Full article
(This article belongs to the Section Nutrition and Metabolism)
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20 pages, 5806 KB  
Article
Development and Validation of a Passive Surveillance System for Early Detection of Pepino Mosaic Virus in Commercial Greenhouse Facilities
by Hester Roberts, David W. Waite, Subuhi Khan, Stella Veerakone, Joe Tang and Jeremy R. Thompson
Viruses 2026, 18(8), 866; https://doi.org/10.3390/v18080866 - 7 Aug 2026
Abstract
The use of environmental nucleic acid (eNA), both DNA and RNA, as a means for surveillance has been a fixture in the scientific literature for many years. The application of environmental screening for genomic signatures of organisms of interest—particularly those of diagnostic concern—is [...] Read more.
The use of environmental nucleic acid (eNA), both DNA and RNA, as a means for surveillance has been a fixture in the scientific literature for many years. The application of environmental screening for genomic signatures of organisms of interest—particularly those of diagnostic concern—is a promising yet still under-utilised tool for sample screening. While the literature tends to focus on the use of high-throughput sequencing (HTS) to detect organisms of interest using metagenomic or metatranscriptomic sampling, this approach is not cost-competitive with more traditional targeted molecular test methods. Consequently, eNA sampling still has not gained significant traction in practical settings despite its popularity in ecological research. To address these issues in a biosecurity context, we report here the development of a testing protocol to monitor irrigation water for the presence of pepino mosaic virus (PepMV) that also includes an endogenous Sphingomonas control. We employed passive sampling through the immersion of filtering devices into the water system at three commercial growing operations at two time points to collect samples with minimal hands-on effort, while simultaneously developing and validating molecular methods for the recovery of RNA competent for both PCR and high-throughput sequencing. We demonstrate not only the ability to detect PepMV from water collections, but also that the method is robust to the accumulation of non-target material and does not lose signal if viruses are only transiently present in the water system. Finally, we developed a capsid-integrity pre-treatment protocol for differentiating between intact and denatured (non-viable) virus particles during PCR testing. This work presents a low-cost and low-effort technique for proactive screening of commercial greenhouse facilities to facilitate early detection of harmful crop pests and pathogens. Full article
(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)
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16 pages, 571 KB  
Article
Vickers Hardness and Microleakage of Coated Glass-Hybrid and High-Viscosity Glass Ionomer Systems in Thermocycled Conservative Class II Cavities: An In Vitro Study
by Chau Bao Ho, Truong Thien Tran and Lan Thi-Quynh Ngo
Dent. J. 2026, 14(8), 499; https://doi.org/10.3390/dj14080499 - 7 Aug 2026
Abstract
Background/Objectives: Glass-hybrid and high-viscosity glass ionomer systems were developed to address limitations of conventional glass ionomer cements. This in vitro study compared post-thermocycling Vickers hardness and microleakage of a coated glass-hybrid system and a coated high-viscosity glass ionomer system in conservative Class [...] Read more.
Background/Objectives: Glass-hybrid and high-viscosity glass ionomer systems were developed to address limitations of conventional glass ionomer cements. This in vitro study compared post-thermocycling Vickers hardness and microleakage of a coated glass-hybrid system and a coated high-viscosity glass ionomer system in conservative Class II cavities. Methods: Thirty extracted human maxillary first premolars each received both systems in standardized mesio-occlusal and disto-occlusal cavities, enabling paired within-tooth comparisons. Following thermocycling and methylene blue immersion, Vickers hardness was measured on polished restoration cross-sections at occlusal and gingival locations. Microleakage was quantified using a continuous microleakage index and ordinal dye penetration scores. Results: The EQUIA Forte HT system had a higher tooth-level mean Vickers hardness than the Gold Label IX Extra system (95.05 ± 6.58 HV vs. 91.33 ± 7.50 HV), with a mean paired difference of 3.72 HV (95% CI, 0.32 to 7.11; p = 0.033; Cohen’s dz = 0.41, 95% CI, 0.03 to 0.78). The location-specific mixed model also showed an effect of restorative system (p = 0.025), whereas neither testing location nor the system × location interaction was significant. No significant between-system difference was detected for the microleakage index or for either ordinal dye penetration score. Conclusions: Within the limitations of this in vitro study, the EQUIA Forte HT system had a modestly higher post-thermocycling tooth-level mean Vickers hardness than the Gold Label IX Extra system, although the clinical relevance of the difference remains uncertain. No between-system differences were detected in dye penetration outcomes. Full article
(This article belongs to the Section Dental Materials)
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19 pages, 8776 KB  
Article
Dual Metabolic Targeting of Cancer: Lessons from Metformin and 2-Deoxy-D-Glucose Combinations
by Vesna Zeljković, Slaviša Minić, Marko Mladenović, Dejan Milenković, Zoran Marković, Tanja V. Soldatović, Vanja Kunkin and Maja Karaman
Cancers 2026, 18(16), 2537; https://doi.org/10.3390/cancers18162537 - 7 Aug 2026
Abstract
Background: Metabolic reprogramming enables cancer cells to adapt to energetic stress and sustain proliferation. Simultaneous inhibition of glycolysis and mitochondrial respiration has emerged as a promising strategy to overcome metabolic plasticity. This study evaluated the antiproliferative effects of the glycolytic inhibitor 2-deoxy-D-glucose [...] Read more.
Background: Metabolic reprogramming enables cancer cells to adapt to energetic stress and sustain proliferation. Simultaneous inhibition of glycolysis and mitochondrial respiration has emerged as a promising strategy to overcome metabolic plasticity. This study evaluated the antiproliferative effects of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) alone and in combination with metformin in human cancer cell lines. Methods: Human cervical carcinoma (HeLa), lung adenocarcinoma (A549), colorectal adenocarcinoma (HT-29), and normal lung fibroblasts (MRC-5) were treated with 2-DG or metformin individually, or with metformin in the presence of a fixed concentration of 2-DG (1 mM). Cell viability was assessed using the sulforhodamine B assay after 24 and 48 h. IC50 values were calculated by nonlinear regression, Dose Reduction Index (DRI) analysis evaluated sensitization to metformin, and molecular docking was performed to investigate interactions with selected metabolic targets. Results: Both 2-DG and metformin inhibited cell proliferation in a concentration- and time-dependent manner. HeLa cells were the most sensitive to glycolytic inhibition, while A549 and HT-29 cells showed moderate susceptibility. Co-treatment with 2-DG significantly enhanced metformin activity, reducing its IC50 in HeLa cells from 6.04 to 2.00 mM after 24 h and from 2.28 to 1.56 mM after 48 h. DRI analysis demonstrated increased sensitivity to metformin in all cancer cell lines, particularly HT-29 and A549, whereas normal MRC-5 fibroblasts remained comparatively less affected. Molecular docking revealed favorable binding of both 2-DG and metformin to proteins involved in cellular energy metabolism. Conclusions: Combined inhibition of glycolysis and mitochondrial respiration potentiates the antiproliferative effects of metformin, increases metabolic vulnerability in cancer cells, and is supported by molecular docking evidence of interactions with metabolic targets, while showing limited toxicity toward normal fibroblasts. These findings support dual metabolic targeting as a promising therapeutic strategy and warrant further mechanistic and in vivo studies. Full article
(This article belongs to the Special Issue Metabolism and Precision Oncology)
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18 pages, 6183 KB  
Article
Mating-Induced Behavioral Changes in Female Drosophila Are Modulated by Serotonin
by Simón Guerra-Ayala, Antonella Cortés-Henott, Paula Amado-Hinojosa, Marcia González-Teuber, Ivana Gajardo and Jorge M. Campusano
Int. J. Mol. Sci. 2026, 27(16), 7070; https://doi.org/10.3390/ijms27167070 - 7 Aug 2026
Abstract
Mating influences the physiology of female animals and induces changes in behaviors associated with securing resources for their offspring. Modulatory neurotransmitters are known to adjust behavioral responses of animals according to environmental cues and internal physiological states. In that regard, it has been [...] Read more.
Mating influences the physiology of female animals and induces changes in behaviors associated with securing resources for their offspring. Modulatory neurotransmitters are known to adjust behavioral responses of animals according to environmental cues and internal physiological states. In that regard, it has been shown that serotonin (5-HT) modulates some post-mating behavioral features in Drosophila. However, it remains unknown whether serotonin regulates post-mating social behavior or responses to food cues in flies, which are among several behaviors that serve to secure their survival and reproduction. Here, we report a behavioral paradigm, the yeast-response test (YRT), for exploring locomotor and social behavioral changes in groups of virgin and mated females using yeast odor as a naturalistic food signal. Using this setup, we found that exposure to yeast odor increases social interactions in mated but not virgin females under non-aversive conditions and that these responses are suppressed at aversive temperatures. Furthermore, chronic impairment of serotonin transporter function reverses the social behavioral response to food odor in mated females, without affecting their olfactory capacity. Whole-brain 5-HT content, as well as histone serotonylation, were unchanged between virgin and mated females, suggesting that 5-HT contribution to these changes is mediated at a circuit level rather than by global neuromodulatory mechanisms. Consistent with this idea, silencing serotonin projection neurons (SPNs) selectively abolished mating-induced changes in social behavior without affecting the locomotor effects. These results provide further support for data in the literature showing that SPNs belong to a discrete circuit underlying social behaviors in female flies. Together, these results support a model in which serotonergic signaling shapes post-mating behavior in Drosophila through functionally segregated neural circuits. Full article
(This article belongs to the Special Issue Drosophila: A Versatile Model in Biology and Medicine—3rd Edition)
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20 pages, 419 KB  
Article
Lactobacillus casei TH14 and Hydrolysable Tannin as Corn Silage Additives Modify In Vitro Rumen Fermentation and Reduce Methane Production
by Rittikeard Prachumchai and Anusorn Cherdthong
Animals 2026, 16(16), 2447; https://doi.org/10.3390/ani16162447 - 7 Aug 2026
Abstract
This study evaluated L. casei TH14 (TH14) and two levels of hydrolysable tannin (HT; sweet chestnut, Castanea sativa) as corn ensiling additives, hypothesising that their combination would improve fermentation quality and reduce in vitro CH4. Whole-plant corn was ensiled for [...] Read more.
This study evaluated L. casei TH14 (TH14) and two levels of hydrolysable tannin (HT; sweet chestnut, Castanea sativa) as corn ensiling additives, hypothesising that their combination would improve fermentation quality and reduce in vitro CH4. Whole-plant corn was ensiled for 21 days in a completely randomised design (seven treatments, four replicates) combining Molasses, TH14, and HT at 20 or 40 g/kg DM. Silage pH was significantly affected by treatment (p < 0.01), with T4 reaching the lowest final pH (3.83), whereas the primary nutrients (DM, OM, CP, and NDF) were unchanged (p > 0.05). Hydrolysable tannin reduced ruminal NH3-N at 24 h (11.12 vs. 13.06 mg/dL; p < 0.05) and, at 40 g/kg DM, lowered CH4 by 50.0% at 24 h (2.45 vs. 4.90 mL/g DM; p < 0.01) in a dose-dependent manner, accompanied by a higher propionate proportion and a lower acetate-to-propionate ratio (p < 0.01). Independent of tannin, TH14 reduced CH4 by 12.7% (p < 0.05). Digestibility was transiently reduced at 24 h but unaffected at 48 h (p > 0.05). Corn silage with HT at 40 g/kg DM, alone or combined with TH14, is a promising strategy to mitigate CH4 without impairing nutrient digestibility. Full article
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13 pages, 2582 KB  
Article
The Effect of Different Surface Treatments on the Color and Translucency of Zirconia: An In Vitro Study
by Khaled M. AlZahrani, Khalid Mohammed Alnajjar, Lamia Yahya M. Alshowail, Maram Fahad Almasri, Daliah Ali Alshehri, Lulu Turki Alammar and Ghadah Saad Alazmi
Prosthesis 2026, 8(8), 84; https://doi.org/10.3390/prosthesis8080084 - 7 Aug 2026
Abstract
Background/Objectives: To compare the effects of different surface treatments on the color and translucency of three types of zirconia ceramics. Methods: Ninety CAD/CAM-milled zirconia disks (10 mm diameter, 1 mm thickness) were fabricated from Cercon HT (3-YTZP), IPS e.max ZirCAD MT (4-YTZP), and [...] Read more.
Background/Objectives: To compare the effects of different surface treatments on the color and translucency of three types of zirconia ceramics. Methods: Ninety CAD/CAM-milled zirconia disks (10 mm diameter, 1 mm thickness) were fabricated from Cercon HT (3-YTZP), IPS e.max ZirCAD MT (4-YTZP), and Cercon XT (5-YTZP). Baseline CIE Lab* coordinates were measured using a digital spectrophotometer. The disks underwent one of three surface treatments: 50 µm alumina air-particle abrasion (AAA), Zircos-E etching (ZE), or 100 µm glass bead air-particle abrasion (GBA). Post-treatment CIE Lab* measurements were obtained, and color change (ΔE00, CIEDE2000) and translucency change (ΔTP00) were calculated. Results: Regarding color change (ΔE00), 50 µm AAA produced the greatest change, followed by ZE, while GBA caused the smallest change. Surface treatment and its interaction with material type were found to exert a significant effect, whereas material type alone was not significant. Cercon XT showed the highest numerical ΔE00 value among the materials, although the difference was not statistically significant. All ΔE00 values were below the clinical acceptability threshold (<1.8). No significant effects of surface treatment, material type, or their interaction were observed for translucency change (ΔTP00) after surface treatment. Baseline translucency values (TP00) differed significantly, with Cercon XT being the most translucent, followed by ZirCAD MT and Cercon HT, but these differences did not result in significant ΔTP00 changes post treatment. Conclusions: Surface treatments and their interaction with material type significantly affected zirconia color change, with 50 µm alumina air-particle abrasion producing the most pronounced effect. Material type alone did not significantly influence ΔE00, though Cercon XT showed the highest numerical value. Translucency change (ΔTP00) after treatment was unaffected by surface treatment or material–treatment interaction. Full article
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28 pages, 10884 KB  
Article
Diminished Maternal Tryptophan Leads to Sexually Dimorphic Differences in the Placenta–Brain Axis
by Rosalind T. B. Herrington, Zhen Lyu, Sarah E. Seda, Emmett E. Boling, Andrea K. Goldstein, Nathan J. Bivens, Zhentian Lei, Tanhaul Islam, Lloyd W. Sumner, Trupti Joshi and Cheryl S. Rosenfeld
Nutrients 2026, 18(15), 2575; https://doi.org/10.3390/nu18152575 - 6 Aug 2026
Abstract
Background: Tryptophan (Trp) is critical to mothers and their conceptuses, and this amino acid is the precursor to serotonin (5-HT). 5-HT modulates placenta function and fetal neurodevelopment. It is not clear if the placenta directly synthesizes 5-HT or uses the serotonin transporter (SERT/ [...] Read more.
Background: Tryptophan (Trp) is critical to mothers and their conceptuses, and this amino acid is the precursor to serotonin (5-HT). 5-HT modulates placenta function and fetal neurodevelopment. It is not clear if the placenta directly synthesizes 5-HT or uses the serotonin transporter (SERT/Slc6a4) to accrue 5-HT from the dam. The hypothesis tested herein is that reduction in maternal Trp leads to reductions in maternal Trp, 5-HT, and 5-hydroxy-3-indoleacetic acid (5-HIAA, metabolite of serotonin) and reductions in these metabolites within the placenta and fetal brain of female and male conceptuses. Methods: Female mice were placed on a reduced tryptophan (Trp) diet (0.1%) or control diet (0.2%). Diets were provided for two weeks prior to breeding (periconception period) until conceptuses were collected at approximately 12.5 days post-coitus (dpc). Results: While no reductions in maternal Trp and 5-HT were observed, both metabolites were significantly reduced in the placenta and fetal brain of male and female conceptuses (p < 0.05). Female conceptuses were susceptible to reductions in maternal Trp with 549 and 29 transcripts altered in the female placenta and fetal brain, respectively, of reduced Trp dams compared to control dams. Transcriptomic changes, such as reduced expression in Slc6a4 and Slc6a19 (transporter for Trp), in placenta of female conceptuses correlated with reductions in Trp and 5-HT amounts. Conclusions: Findings might have clinical importance to pregnant women as they reveal even subtle reductions in one amino acid profoundly influence conceptus development and might lead to sexual disparity in risk for later diseases, including neurobehavioral disorders. Full article
(This article belongs to the Special Issue Women’s Special Issue Series: Nutrients)
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15 pages, 3014 KB  
Article
Age-Stratified Transcriptomic Profiling Identifies CEMIP as a Candidate Biomarker in Early-Onset Colorectal Cancer and Reveals an Association with PTCH1-Related Hedgehog Signaling
by Chung-Ying Lee, Hsu-Jui Pan, Yu-Cheng Lee, Hieu Duc Nguyen, Yi-Chun Ni, Ke Xin Yee, Man Thi Nguyen, Yung-Fu Wu and Kuen-Haur Lee
Genes 2026, 17(8), 922; https://doi.org/10.3390/genes17080922 - 4 Aug 2026
Viewed by 110
Abstract
Background/Objectives: Early-onset colorectal cancer (EOCRC), defined as colorectal cancer diagnosed before 50 years of age, is increasing worldwide and may exhibit molecular features distinct from late-onset colorectal cancer (LOCRC). This study aimed to identify EOCRC-associated genes and evaluate the functional relevance of the [...] Read more.
Background/Objectives: Early-onset colorectal cancer (EOCRC), defined as colorectal cancer diagnosed before 50 years of age, is increasing worldwide and may exhibit molecular features distinct from late-onset colorectal cancer (LOCRC). This study aimed to identify EOCRC-associated genes and evaluate the functional relevance of the leading candidate. Methods: Public transcriptomic datasets were used for age-stratified candidate-gene discovery and validation. Overall survival analysis prioritized candidates, followed by loss-of-function studies and pathway-focused analyses in colorectal cancer cell lines. Results: CEMIP, NKD2, and FOXQ1 were elevated in the EOCRC groups in the discovery and integrated validation analyses. Among them, only CEMIP was significantly associated with poorer overall survival. HCT116 and HT29 cells showed relatively high endogenous CEMIP expression, and CEMIP knockdown reduced relative viable cell biomass and migration in wound-healing and Transwell assays. CEMIP-associated transcripts were enriched in several pathways, including Hedgehog, Wnt/β-catenin, and TGF-β signaling. In TCGA colon adenocarcinoma samples, CEMIP correlated most strongly with PTCH1; however, the correlations with other Hedgehog components were weak or absent. CEMIP silencing decreased PTCH1 and GLI1 transcripts while increasing SMO, suggesting a coordinated but non-linear relationship. Conclusions: CEMIP is an EOCRC-associated candidate biomarker and a functional contributor to colorectal cancer cell viability and migration. Its relationship with PTCH1-related Hedgehog signaling is exploratory and warrants direct mechanistic validation. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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53 pages, 3961 KB  
Review
Pharmacological Switching in Minor Phytocannabinoids: A Mechanistic Framework for Compound–Indication Matching and Precision Neurotherapeutic Development
by Amina M. Bagher
Pharmaceuticals 2026, 19(8), 1226; https://doi.org/10.3390/ph19081226 - 4 Aug 2026
Viewed by 216
Abstract
Background: Minor phytocannabinoids engage CB1 and CB2 receptors, as well as broader receptors and ion-channel targets. However, fragmented evidence limits translation into central nervous system (CNS) therapeutics. This review introduces pharmacological switching, defined as a dose-, state-, or model-dependent shift [...] Read more.
Background: Minor phytocannabinoids engage CB1 and CB2 receptors, as well as broader receptors and ion-channel targets. However, fragmented evidence limits translation into central nervous system (CNS) therapeutics. This review introduces pharmacological switching, defined as a dose-, state-, or model-dependent shift in the dominant determinant of a compound’s net effect that reverses the direction, rather than merely the magnitude, of that effect on a defined functional endpoint, as a framework for compound–indication matching. Unlike biased agonism, which redistributes downstream coupling without reversing direction, switching requires directional reversal between or within receptor systems. Methods: This narrative review integrates receptor pharmacology, preclinical CNS disease-model data, early-phase clinical evidence, and pharmacokinetics identified through a structured literature search. Results: Three mechanistic axes recurred: PPARγ/CB2/Nrf2-linked neuroinflammatory modulation; TRP/GABAA/5-HT1A-linked control of neuronal excitability; and low-efficacy CB1 antagonism with 5-HT1A potentiation. Their expression was context-dependent: tetrahydrocannabivarin is reported to shift from CB1 antagonism toward partial agonism as receptor occupancy rises, cannabidiolic acid shows stress-conditional anxiolytic and antiemetic activity, and cannabigerolic acid displays seizure-model-dependent bidirectionality. No instance yet meets all five defining criteria; each is graded provisional or proposed pending systematic testing. Human evidence remains limited: inconclusive cannabidivarin efficacy in epilepsy and neuropathic pain, proof-of-mechanism neuroimaging in autism, and early tetrahydrocannabivarin safety data. Conclusions: Minor phytocannabinoids are pharmacologically diverse but clinically underdeveloped. A tiered, biomarker-guided framework is proposed to match compound–indication pairs to the doses, formulations, and subgroups most likely to express their therapeutic pharmacology. Full article
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25 pages, 5050 KB  
Article
Multi-Targeted Neuroprotection by Areca catechu Against Cisplatin-Induced Neurotoxicity: Cellular, Caenorhabditis elegans, and Metabolomic Evidence
by Kishore K. Kumaree, Clerance Su Yee Cheong, Kanika Verma, Kartina Nadyani, Nureesun Mahamud, Pornpimol Mahamad, Tewin Tencomnao, Anchalee Prasansuklab and James M. Brimson
Int. J. Mol. Sci. 2026, 27(15), 7004; https://doi.org/10.3390/ijms27157004 - 4 Aug 2026
Viewed by 234
Abstract
Cisplatin is an effective platinum-based chemotherapeutic agent used to treat a variety of cancers. However, its clinical utility is limited by dose-dependent neurotoxicity, yet no approved neuroprotective strategy currently exists. Our integrated cellular, metabolic, and in vivo approaches unraveled the neuroprotective potential of [...] Read more.
Cisplatin is an effective platinum-based chemotherapeutic agent used to treat a variety of cancers. However, its clinical utility is limited by dose-dependent neurotoxicity, yet no approved neuroprotective strategy currently exists. Our integrated cellular, metabolic, and in vivo approaches unraveled the neuroprotective potential of Areca catechu ethyl acetate extract (AC-EA) against cisplatin-induced neurotoxicity. Importantly, AC-EA did not reduce cisplatin-induced cytotoxicity in A549 lung cancer cells. In HT22 hippocampal neurons, AC-EA restored cell viability, suppressed reactive oxygen species generation, preserved mitochondrial-associated fluorescence, and attenuated phosphorylated histone H2AX (γH2AX)-marked DNA damage. AC-EA was associated with increased pNRF2 expression, consistent with activation of NRF2-dependent antioxidant signaling, suppressed inducible nitric oxide synthase iNOS (inducible nitric oxide synthase )-mediated neuroinflammation, and prevented the depletion of total AKT (protein kinase B) protein. Untargeted metabolomics and Caenorhabditis elegans survival assays were performed for mechanistic and in vivo validation. Metabolomics data showed restoration of several critical amino acids, including L-tyrosine and β-alanine, disrupted by cisplatin. Moreover, C. elegans studies confirmed in vivo activation of antioxidants via the SKN-1/GST-4 (glutathione S-transferase 4) pathway. While AC-EA shows neuroprotective potential, arecoline’s toxicity demands caution. To our knowledge, this is the first study to demonstrate the neuroprotective activity of A. catechu against cisplatin-induced neurotoxicity, laying the foundation for developing plant-derived adjunct therapies for chemotherapy-associated neuropathy. Full article
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18 pages, 7946 KB  
Article
Effects of Sea Buckthorn Flavonoids on Growth Performance, Blood Biochemical Indexes, Rumen Fermentation and Rumen Bacteria of Hu Sheep Fed with High-Concentrate Diet
by Junlong Zhang, Caixia Shi, Wenguang Zhang, Risu Na, Mingjuan Gu, Lin Zhu, Jie Wang, Haoyuan Tian, Xin Li, Jing Jin, Liye Xiong, Tiankai Wang and Shuhan Zhao
Animals 2026, 16(15), 2403; https://doi.org/10.3390/ani16152403 - 4 Aug 2026
Viewed by 219
Abstract
This study evaluated the effects of dietary sea buckthorn flavonoid (SF) supplementation on growth performance, serum biochemical, antioxidant, and immune indices, rumen fermentation, and ruminal bacterial composition in Hu sheep fed a high-concentrate diet. Thirty 6-month-old fattening Hu sheep were randomly assigned to [...] Read more.
This study evaluated the effects of dietary sea buckthorn flavonoid (SF) supplementation on growth performance, serum biochemical, antioxidant, and immune indices, rumen fermentation, and ruminal bacterial composition in Hu sheep fed a high-concentrate diet. Thirty 6-month-old fattening Hu sheep were randomly assigned to a high-concentrate control diet (HC) or the same diet supplemented with 0.30% SF (HT; n = 15 per group) for 45 days. Compared with the HC group, SF supplementation increased average daily gain (p = 0.04) and reduced the feed conversion ratio (p = 0.01) without affecting average daily feed intake. Serum total protein, alanine aminotransferase, total antioxidant capacity, IgA, IgG, IL-2, IL-8, and IL-1β were increased in the HT group (p ≤ 0.05). Ruminal acetate and valerate concentrations increased (p = 0.01 and p = 0.03, respectively), and total volatile fatty acid concentration showed an increasing tendency (p = 0.06), whereas rumen pH was unaffected. The relative abundances of Succiniclasticum and Acidaminococcus increased in the HT group (p < 0.05), indicating modulation of specific ruminal bacterial taxa. In conclusion, supplementation with 0.30% SF improved growth efficiency, antioxidant status, selected immune indices, and specific rumen fermentation and bacterial responses in Hu sheep fed a high-concentrate diet. However, the isolated increase in serum alanine aminotransferase may indicate hepatic metabolic adaptation or mild liver stress. Dose–response and time-course studies incorporating liver-specific biomarkers and histopathological evaluation are required to clarify the hepatic safety of sea buckthorn flavonoid supplementation. Full article
(This article belongs to the Special Issue Feed Additives in Animal Nutrition: 2nd Edition)
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15 pages, 264 KB  
Article
Graft-Specific Neuromuscular Responses and EMG Activities During Running Before and After Running-Induced Fatigue in Individuals with ACL Reconstruction
by Heidar Sajedi, Mahsa Habibi, AmirAli Jafarnezhadgero, Ebrahim Piri, Kate E Webster and Valdeci Carlos Dionisio
Sensors 2026, 26(15), 4904; https://doi.org/10.3390/s26154904 - 3 Aug 2026
Viewed by 149
Abstract
Background: Fatigue during intense activity challenges the neuromuscular system and can reveal deficits not evident during lower-demand functional tasks. In individuals with anterior cruciate ligament reconstruction (ACLR), differences in graft source may be associated with graft-specific neuromuscular adaptations. Although fatigue-related neuromuscular deficits after [...] Read more.
Background: Fatigue during intense activity challenges the neuromuscular system and can reveal deficits not evident during lower-demand functional tasks. In individuals with anterior cruciate ligament reconstruction (ACLR), differences in graft source may be associated with graft-specific neuromuscular adaptations. Although fatigue-related neuromuscular deficits after ACLR have been reported, few studies have examined whether these responses differ according to graft type during running. This study investigated the effects of running-induced fatigue on lower-limb muscle activity during the stance phase in ACLR patients with different graft types, compared with healthy controls. Methods: Fifty-three active males were allocated into four groups: single-bundle hamstring tendon (SB-HT), double-bundle hamstring tendon (DB-HT), allograft, and healthy controls. Participants completed a treadmill-based fatigue protocol that was terminated when they reached a Borg score > 17, which served as the primary criterion for confirming a high level of perceived fatigue. Heart rate ≥ 85% of estimated maximum heart rate was recorded as a complementary physiological indicator of high-intensity exertion. Electromyography (EMG) amplitudes of eight lower-limb muscles were recorded during the early and late stance phases of running, before and after fatigue. A two-way mixed-model ANOVA evaluated the effects of graft type and fatigue condition. Results: Fatigue reduced semitendinosus (p = 0.042, ηp2 = 0.091) and gluteus medius (p < 0.001, ηp2 = 0.442) activation during early stance regardless of group. Late-stance group effects were significant for the tibialis anterior, gastrocnemius, rectus femoris, biceps femoris, semitendinosus, and gluteus medius (p ≤ 0.05). Across stance phases, the SB-HT group showed greater hamstring and gluteus medius activation than healthy controls (p = 0.003–0.041), while the allograft group showed greater tibialis anterior, gastrocnemius, and rectus femoris activation during late stance (p = 0.005–0.043). The only significant group × fatigue interaction was observed for vastus medialis (p = 0.002, ηp2 = 0.279), reflecting a fatigue-related reduction in the DB-HT group. Conclusions: Graft type was associated with distinct lower-limb EMG activation patterns during running after ACLR. Fatigue revealed a DB-HT-specific reduction in vastus medialis activation, while the allograft and SB-HT groups showed different compensatory activation profiles. These findings suggest that graft-specific neuromuscular adaptations during fatigue should be considered when developing rehabilitation protocols to improve functional stability and future joint health. Full article
(This article belongs to the Special Issue Advanced Sensing Technologies in Sports Biomechanics)
22 pages, 3167 KB  
Article
Artificial Intelligence- and Machine Learning-Assisted Structure-Based Virtual Screening of Compounds That Target 15PGDH
by Syed Sayeed Ahmad and Inho Choi
Pharmaceutics 2026, 18(8), 957; https://doi.org/10.3390/pharmaceutics18080957 - 3 Aug 2026
Viewed by 167
Abstract
Background: Skeletal muscle (SM) plays a critical role in movement, metabolism, and organ protection, with its maintenance and regeneration relying on muscle satellite (stem) cells (MSCs). Prostaglandin E2 (PGE2) regulates MSCs, but PGE2 levels decline with aging due to increased catabolism by [...] Read more.
Background: Skeletal muscle (SM) plays a critical role in movement, metabolism, and organ protection, with its maintenance and regeneration relying on muscle satellite (stem) cells (MSCs). Prostaglandin E2 (PGE2) regulates MSCs, but PGE2 levels decline with aging due to increased catabolism by 15-hydroxyprostaglandin dehydrogenase (15PGDH), a negative regulator of muscle repair. Methods: This study aimed to employ artificial intelligence and machine learning (ML)-assisted, structure-based screening approaches to identify novel 15PGDH inhibitors. Supervised models (support vector machine, random forest, and XGBoost were trained on curated bioactivity data (IC50 values) from the ChEMBL database and used to virtually screen the Maybridge compound library (~51,000 compounds). Results: The area under the curve (AUC) values of the developed models SVM, RF, and XGBoost were 0.96, 0.99, and 1.00, respectively. Promising inhibitors were further validated using structure-based virtual screening (docking), molecular dynamics simulations (200 ns), and MM-PBSA/GBSA analyses. The top five inhibitors (PD00616, HTS11491, HTS02629, AW00889, and HTS11190) were identified as active (ML analysis) and potential 15PGDH inhibitors based on their subsequent binding affinities, involvement of catalytic residues (Ser138, Tyr151, and Lys155), and complex stability. Additionally, these inhibitors were found to follow the drug-likeness criteria. Conclusions: These findings offer valuable insights for the development of novel therapeutics targeting 15PGDH to combat muscle degeneration and related pathologies, including aging and sarcopenia. Full article
(This article belongs to the Special Issue In Silico Approaches of Drug–Target Interactions)
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