Search Results (23,048)

Background/Objectives: Probiotic interventions are widely used to improve intestinal health; however, comparative evidence on multi-strain formulations with different potencies, particularly when combined with plant-based complexes, remains limited. This study evaluated the effects of two probiotic blends containing phytonutrients: PBP1, comprising Lacticaseibacillus strains, and PBP2, comprising Lacticaseibacillus, Lactobacillus, and Bifidobacterium strains. The effects on bowel function, microbial metabolites, and gut barrier-related markers were investigated. Methods: In this randomized, double-blind, placebo-controlled trial, participants received PBP1, PBP2, or placebo for 8 weeks. Stool patterns (7-day Bristol Stool Form Scale (BSFS) diary), fecal short-chain fatty acids (SCFAs), tryptophan metabolites, zonulin, and gut microbiota were assessed at baseline and Week 8. Efficacy was evaluated by comparing each intervention group with the placebo group. Results: Both PBP1 and PBP2 significantly increased the proportion of normal stool types (BSFS types 3–5) compared with placebo (p < 0.05). Fecal SCFA levels, including acetate, propionate, and butyrate, were significantly increased in both intervention groups. Notably, butyrate levels were significantly elevated compared with placebo. Fecal tryptophan levels decreased, while indole metabolites showed increasing trends, with an inverse correlation observed between tryptophan and indole, particularly in the PBP2 group. Fecal zonulin showed a decreasing trend, with significant reductions in participants with 25.0 ≤ BMI < 30.0 kg/m². Microbiome analysis revealed preserved alpha diversity with selective compositional shifts, including enrichment of Lactobacillus-related taxa. Conclusions: Supplementation with PBP1 and PBP2 improved bowel function and was associated with changes in microbiome-derived metabolites, including SCFAs and tryptophan–indole metabolism, with BMI-dependent changes in barrier markers. These findings suggest a potential role of microbiome-mediated metabolic modulation in intestinal health. Full article

In this article, we propose a novel real-time terrain recognition and slip estimation method for quadruped robots using proprioceptive sensors and temporal convolutional networks (TCNs). As quadruped robots are increasingly deployed in complex environments, accurate terrain understanding is crucial. External sensors can be affected by lighting variations, occlusion, reflective surfaces, and others. To overcome these challenges, we propose a proprioceptive sensing-based complementary perception module with a TCN, enabling reliable real-time terrain recognition while reducing dependence on external perception. The TCN model effectively captures temporal dependencies in sensor signals, enabling precise and robust detection. The framework is validated through extensive real-world experiments and deployed on an embedded edge computing platform for real-time operation. Results show that the proposed TCN method achieves 98.8% recognition accuracy, outperforming the baseline models compared in this study. In addition, this study analyzes how locomotion speed and environmental conditions affect slip in quadruped robots. These findings confirm that quadruped robots can not only recognize terrain types but also detect surface states, enabling safer and more adaptive locomotion. Therefore, the proposed system is a cost-effective, robust, and low-latency solution for real-time terrain recognition, providing a strong foundation for future deployment across more diverse terrains. Full article

Natural killer (NK) cells are crucial components of innate immunity and rapidly eliminate abnormal cells through ligand–receptor signaling without prior sensitization. Vitamin C is known to enhance NK cell function; however, its susceptibility to oxidation may limit its efficacy in NK cell activation. This study evaluated the efficacy of Aptamin C, a stabilized conjugate of vitamin C and an aptamer, in enhancing NK cell activation. In the in vivo randomized placebo-controlled study, 120 participants were randomized to receive either Aptamin C or placebo, and 109 participants were included in the final analysis. Participants received Aptamin C at a dose of 36.057 mg/day or placebo for 4 weeks. The results showed significant increases in NK cell cytotoxicity after 2 and 4 weeks in the Aptamin C group. Additionally, serum levels of cytokines and cytotoxic granules associated with NK cell activity peaked 4 weeks after Aptamin C intake. Subgroup analysis showed that the enhancing effect of Aptamin C on NK cell activity was mainly observed in participants older than 40 years, whereas no significant effects were detected in participants aged <40 years. In the in vitro study, NK-92 cells treated with Aptamin C were compared with NK-92 cells treated with vitamin C. Aptamin C treatment enhanced proliferation, survival, cytotoxicity, and cytotoxic granule production in NK-92 cells compared with vitamin C treatment. These findings indicate that Aptamin C may effectively promote NK cell activation, particularly in middle-aged and older adults, and suggest its potential as an immunomodulatory supplement for supporting NK cell function. Full article

This study evaluated the effects of reducing dietary crude protein (CP) levels and protease supplementation on growth performance, nutrient digestibility, and fecal score in weaned piglets. A total of 200 crossbred weaned piglets (Duroc × [Landrace × Yorkshire]), with an initial body weight (BW) of 6.01 ± 1.14 kg, were used in a 31-day feeding trial. Piglets were assigned to four dietary treatments in a randomized complete block design with 10 replicates per treatment and five piglets per pen. The treatments were as follows: CON, basal diet; TRT1, low-protein diet with CP reduced by 1%; TRT2, low-protein diet with CP reduced by 2%; and TRT3, TRT2 supplemented with 0.1 g/kg protease. Piglets fed TRT2 had lower BW on days 7, 19, and 31 (p < 0.05) and lower average daily gain (ADG) during each growth phase and the overall period compared with CON (p < 0.05). Protease supplementation partially restored BW and ADG. However, average daily feed intake (ADFI), feed conversion ratio (FCR), apparent digestibility of dry matter (DM), nitrogen (N), and energy (E), and fecal score were not affected by dietary treatments (p > 0.05). In conclusion, reducing dietary CP by 2% impaired growth performance in weaned piglets, whereas protease supplementation partially alleviated this negative effect without significantly altering nutrient digestibility or fecal score. Full article

Waste plastic aggregate (WPA) is a promising recycled material for asphalt mixtures, but its polymeric surface can weaken binder adhesion and increase moisture-related damage, even in SBS-modified systems. Therefore, a clear need exists to identify anti-stripping agents that are compatible with WPA, rather than simply increasing WPA content in asphalt mixtures. This study evaluates the interfacial and mixture-scale performance of SBS-modified asphalt mixtures containing two WPA types, namely coarse WPA and fine WPA, treated with three liquid anti-stripping agents: amine-based agent (AS-Am), organosilane coupling-type adhesion promoter (AS-OS), and ester/surfactant-based wetting agent (AS-Es). The novelty of this study lies in selecting the anti-stripping system based on WPA–binder adhesion compatibility and validating it through moisture, rutting, rheological, and fracture performance. Binder bond strength, tensile bond strength, shear bond strength, indirect tensile strength/tensile strength ratio (ITS/TSR), Hamburg wheel tracking (HWT), multiple stress creep recovery (MSCR), and semi-circular bending (SCB) tests were conducted. AS-OS showed the best overall performance. It increased binder bond strength (BBS) by 52.8% for coarse WPA and 61.5% for fine WPA, while the optimum 0.5% dosage improved tensile bond strength by 81.0% and 97.2%, respectively. AS-OS also increased shear strength by 58.8–68.3% and improved TSR to 89.0% and 86.2%. In HWT, C-OS and F-OS reduced final rut depth by 44.0% and 45.8%, respectively. SCB results further showed higher fracture work, especially for F-OS. The findings indicate that proper anti-stripping chemistry is essential for durable WPA–SBS asphalt mixtures. Full article

This study evaluates the chemical composition and bioactivities of essential oils extracted from the leaves and twigs of Glycosmis lanceolata growing in a natural forest in Vietnam. gas chromatography–mass spectrometry identified 42 and 43 constituents in the leaf and twig oils, respectively. The main compounds in the leaf oil were (E)-β-caryophyllene (10.2%), β-bisabolene (23.7%), and brevifolin (21.3%), while the twig oil was dominated by β-bisabolene (11.6%) and brevifolin (12.7%). Neither oil exhibited inhibitory effects against two beneficial bacterial strains, Bacillus subtilis and Lactobacillus fermentum. In contrast, both oils showed weak antimicrobial activity against four pathogenic bacteria—Staphylococcus aureus, Salmonella enterica, Escherichia coli, and Pseudomonas aeruginosa—and one yeast, Candida albicans, with IC₅₀ values ranging from 2012 ± 118 to 10,593 ± 557 µg/mL. Notably, the twig oil demonstrated pronounced anti-inflammatory activity via inhibition of nitric oxide production (IC₅₀ = 29.7 ± 2.58 µg/mL), whereas the leaf oil showed no detectable activity within the tested concentrations. Similarly, DPPH radical scavenging assays indicated stronger antioxidant activity for the twig oil compared to the leaf oil. These findings provide new insights into the phytochemistry and bioactivities of G. lanceolata essential oils and may support further investigations into their potential applications. Full article

Neurolymphomatosis (NL), a rare manifestation of non-Hodgkin’s lymphoma affecting the peripheral nervous system, remains a diagnostic challenge. This study aimed to define an optimal diagnostic approach for timely and effective identification of NL. We analyzed 559 NL cases from 231 articles published from 1951 to 2022, examining how patient outcomes correlated with various diagnostic modalities, including magnetic resonance imaging (MRI), computed tomography (CT), [¹⁸F]fluorodeoxyglucose positron emission tomography (FDG-PET), electromyography-nerve conduction studies (EMG-NCS), ultrasound, and tissue biopsy when used individually or in combination. Separate analyses were performed in a mutually exclusive fashion to minimize confounding effects from multiple modalities. The results of this investigation revealed that patients with biopsies had a longer time interval from first treatment to progression (Kruskal–Wallis p < 0.0001), survival from diagnosis (overall survival) (p < 0.0001), and survival from symptom onset (p < 0.0001), but not symptom onset to diagnosis (p = 0.2134). Pairwise comparisons of biopsy plus 2, 3, or 4 diagnostic modalities revealed a positive trend for the combination of biopsy + PET + MRI + EMG-NCS. A majority of patients without biopsy had secondary NL. In this non-biopsied population, no diagnostic modality had a significant correlation with outcome. The data collectively indicate that histological confirmation of NL from biopsy was associated with a positive patient outcome. Management of NL patients requires timely testing using PET, MRI, and EMG-NCS to quickly identify a site for image-guided nerve biopsy. Full article

Background: OnabotulinumtoxinA and calcitonin gene-related peptide (CGRP) monoclonal antibodies are widely used for chronic migraine prevention, but comparative real-world evidence on healthcare utilization remains limited. This study aimed to compare the association of onabotulinumtoxinA versus CGRP monoclonal antibodies with acute triptan prescription and migraine-related return visits in patients with chronic migraine. Methods: We conducted a retrospective cohort study using the TriNetX global federated electronic health record database from 2018 to 2024. Adults with chronic migraine who initiated onabotulinumtoxinA or a CGRP monoclonal antibody were matched 1:1 by propensity score. The primary outcomes were time to acute triptan prescription and time to first migraine-related return visit during follow-up. Results: After propensity score matching, 10,140 patients were included in each treatment group. OnabotulinumtoxinA was associated with a lower hazard of acute triptan prescription than CGRP monoclonal antibodies (hazard ratio 0.513, 95% confidence interval 0.481–0.546; p < 0.001), whereas migraine-related return visits were similar between groups (hazard ratio 1.008, 95% confidence interval 0.977–1.039; p = 0.69). Conclusions: In this multicenter real-world analysis, onabotulinumtoxinA was associated with a lower hazard of acute triptan prescription than CGRP monoclonal antibodies, while migraine-related return visits were comparable. These findings reflect treatment-related healthcare utilization patterns in routine practice and should be interpreted considering the limitations of retrospective electronic health record data. Full article

Phytonutrient-enriched prebiotic mixtures (PEPs), composed of phytonutrients and prebiotics serving as substrates for gut microbes, are recognized for their potential to modulate gut microbial metabolic activity. However, direct evidence of enhanced effects following co-administration with probiotics remains limited. Using a three-phase design integrating ex vivo evaluation and clinical validation, we assessed how PEP components influence microbial responses and whether co-administration with probiotics enhances these effects. PEP components increased acetate, butyrate, total short-chain fatty acids (SCFAs), and lactate, with fiber-rich components showing the strongest effects (all q < 0.0001 relative to negative control). Co-treatment with probiotics further enhanced butyrate and total SCFAs in a dose-dependent manner. In a randomized clinical study, all groups showed increases in fecal metabolites, with the combined group exhibiting the greatest increases in butyrate (+6.0 µmol/g, ~1.5-fold, p < 0.05) and total SCFAs (+22.9 µmol/g, ~1.3-fold, p < 0.05). Participants with constipation-type stool patterns shifted toward normal stool types across all groups. These findings support the utility of combined PEP and probiotic interventions for enhancing microbiome-derived metabolic activity. Full article

Acetaminophen (APAP) overdose is a major cause of drug-induced liver injury and remains a widely used model of xenobiotic-induced hepatotoxicity. Oxidative stress, mitochondrial dysfunction, and ferroptosis are key events in APAP-mediated liver damage. In this study, we investigated whether L-menthol pretreatment protects against APAP-induced acute liver injury and explored the underlying mechanisms in vivo and in vitro. Male C57BL/6 mice were pretreated with L-menthol (100 mg/kg/day) for 7 days before APAP challenge (300 mg/kg). L-menthol markedly attenuated hepatic necrosis, inflammatory infiltration, and hepatocyte injury, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, suppressed IL-1β, IL-6, and TNF-α production, restored hepatic glutathione and superoxide dismutase levels, and decreased malondialdehyde accumulation. Transcriptomic analysis revealed significant enrichment of differentially expressed genes in reactive oxygen species- and ferroptosis-related pathways. In APAP-challenged HepG2 cells, L-menthol improved cell viability, preserved mitochondrial ultrastructure, reduced ferrous iron accumulation, was associated with upregulation of Keap1/Nrf2/HO-1/NQO1 pathway-related proteins, and restored GPX4 expression. Collectively, these findings indicate that L-menthol pretreatment attenuates APAP-induced hepatotoxicity, possibly through enhancement of antioxidant defenses and attenuation of ferroptosis-associated changes, supporting its potential as a preventive hepatoprotective small molecule against xenobiotic-induced liver injury. Full article

Background/Objectives: Assessment of cognitive function in patients with dementia is often hindered by functional and environmental barriers. Although caregiver reports are an alternative source, their clinical utility for estimating patients’ cognitive function remains uncertain. This study aimed to estimate cognitive function using caregiver-reported data combined with patient demographics and to evaluate its clinical utility. Methods: This retrospective cross-sectional study enrolled participants who visited a memory clinic and completed the Montreal Cognitive Assessment (MoCA) for cognitive assessment, together with caregiver-reported questionnaires for activities of daily living (ADL) and neuropsychiatric symptoms (NPS). Multivariable linear regression models were constructed to predict the MoCA score, with Model 1 including demographics, ADL, and NPS as covariates and Model 2 further incorporating clinical diagnosis. The intraclass correlation coefficient, Bland–Altman analysis, and regression error characteristic curves were assessed. Results: Among 2650 participants (56.5% women; mean age, 70.4 years), the NPS variable was excluded from both models. Model 1, which included demographics and ADL, explained 65.4% of the variance, whereas Model 2, which incorporated clinical diagnosis, explained 75.9%. Model 2 yielded an intraclass correlation coefficient of 0.853, compared to 0.778 for Model 1. At a 4-point error tolerance, Model 2 yielded an accuracy of 75.5%. Bland–Altman biases were near zero, with 95% limits of agreement of approximately ±7 points for Model 2. Conclusions: MoCA scores can be estimated using caregiver-reported ADL scores, demographics, and clinical diagnosis. NPS scores provided no additional predictive value when these factors were included. These models provide valid quantitative tools for indirect cognitive assessment when in-person testing is impossible. Full article

Background/Objectives: Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Despite advances in treatment, outcomes for advanced CRC remain unsatisfactory due to uncontrolled proliferation, metastasis, and recurrence. This study investigated the anti-cancer effects of KMU-11342, an indolin-2-one-based multi-protein kinase inhibitor with previously reported anti-inflammatory properties, in human colorectal cancer models. Methods: The anti-cancer effects of KMU-11342 were evaluated in colorectal cancer cells and further investigated in three-dimensional (3D) spheroid and patient-derived organoid models. Cell proliferation, migration, apoptosis, and cell cycle progression were assessed. Kinase activity profiling and molecular docking analyses were performed to identify potential targets and characterize the underlying signaling pathways. Results: KMU-11342 significantly inhibited the proliferation and migration of CRC cells. It reduced CRC cell density by 58.9% and 83.3% at 0.5 and 1 μM, respectively. These effects were accompanied by G2/M cell cycle arrest and apoptotic cell death. In 3D models, spheroid formation was markedly reduced and stemness-related characteristics were diminished. Patient-derived CRC organoids also showed decreased viability, exhibiting 38.6% and 77.4% reductions at 1 and 2 μM, respectively. These effects were observed in a dose-dependent manner in both two-dimensional (2D) and 3D colorectal cancer models. Kinase activity profiling and molecular docking analyses identified glycogen synthase kinase 3 beta (GSK3β) and cyclin-dependent kinase 1 (CDK1) as potential mediators of the anti-cancer effects of KMU-11342 through the p53/nuclear factor kappa B (NF-κB) and FoxO1 signaling axes, respectively. Conclusions: KMU-11342 exhibits potent anti-tumor activity against CRC through suppressing proliferation, migration, and stemness in both 2D and 3D models, including patient-derived organoids. Its effects may be mediated, at least in part, through modulation of GSK3β and CDK1 via the p53/NF-κB and FoxO1 signaling pathways. Full article

Objectives: Dyslipidemia is a major driver of cardiovascular disease (CVD), causing a global economic burden. Statins are the mainstay for reducing LDL-C, with pitavastatin (PIT) being the newest-generation statin, showing non-inferior efficacy compared with potent statins. This study aims to assess the cost-effectiveness of pitavastatin in comparison with atorvastatin (ATOR) and rosuvastatin (ROS). Method: The PubMed, Cochrane, and Embase databases were searched to identify full or partial economic evaluations through 19 November 2025. Our primary outcome is the incremental cost-effectiveness ratio (ICER), with health outcomes measured by quality-adjusted life years (QALYs) or percentage reduction in LDL-C. Regarding quality assessment, the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 tool was applied. The Revised Cochrane Risk of Bias Tool for Randomized Trials (RoB 2) checklist and Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) were performed for RCTs and non-RCT risk assessments, respectively. Result: Five studies were synthesized. One model-based analysis over a lifetime revealed that PIT was less expensive but generated slightly fewer QALYs than ATOR and was dominated by ROS. Four within-trial CEAs with follow-up ≤12 months found that for each 1% reduction in LDL-C, PIT was generally more economical than low-dose ATOR but consistently more costly than ROS. Conclusions: Because of the small number and heterogeneity of studies, it is not possible to draw firm conclusions about the cost-effectiveness of PIT. Further model-based analyses with an adequate sample size and comprehensive costing are needed to clarify the economic role of PIT. Full article

Background: Foot degloving injuries are associated with extensive soft-tissue disruption, compromised perfusion, and a high risk of flap necrosis. Hyperbaric oxygen therapy (HBOT) is known to enhance tissue oxygenation and support flap survival; however, its application in pediatric patients may be limited due to poor cooperation, intolerance to chamber-based treatment, and limited accessibility. Case Presentation: A 7-year-old girl presented with a crush injury to the left foot after being run over by a vehicle, resulting in severe soft-tissue damage. Evaluation revealed a dorsal foot degloving injury, a proximal phalanx fracture of the great toe, and dislocations of the fourth proximal interphalangeal and fifth distal interphalangeal joints. Emergency surgery included open reduction, K-wire fixation, debridement, and artificial dermal grafting using Pelnac. On postoperative day 1, the flap showed signs of compromised perfusion. As HBOT was not feasible, topical oxygen therapy using Natrox was applied continuously for 17 days. Serial wound assessments demonstrated gradual improvement in flap viability. Although ischemic changes developed in the toes, necrosis remained superficial and was successfully managed with local debridement and dressings. Residual skin defects with partial necrosis were treated with split-thickness skin grafting, which healed without major complications. The patient resumed ambulation after splint removal. Conclusions: In pediatric patients with compromised flaps in whom HBOT is not feasible, topical oxygen therapy may serve as a practical adjunctive treatment option. Although its independent effect cannot be established in a single case, this report suggests its potential role in flap salvage and in limiting tissue necrosis. Full article

This study characterized the basic structure of partridge tea leaves polysaccharides and comparatively analyzed the in vitro lipid-lowering activity of total partridge tea polysaccharide (PTPS) and its two purified homogeneous fractions, namely PTPS-I (13,560 Da) and PTPS-III (30,935 Da). In terms of structural composition, PTPS-I and PTPS-III share identical monosaccharide types but differ significantly in monosaccharide proportions, glycosidic linkages and backbone structures. In vitro experiments demonstrated that PTPS, PTPS-I, and PTPS-III could effectively reduce intracellular lipid levels and oxidative stress in free fatty acids (FFA)-injured L02 cells and alleviate the decline of mitochondrial membrane potential in damaged hepatocytes. At the high concentration of 400 μg/mL, PTPS-III showed a superior effect in reducing triglyceride (TG) content compared with the other two samples, with the value reaching 0.31 ± 0.024 mmol/mg prot. Additionally, 400 μg/mL PTPS markedly decreased total cholesterol (TCHO) content and enhanced superoxide dismutase (SOD) activity, which were 0.55 ± 0.039 mmol/mg prot and 29.92 ± 0.22 μmol/mg prot, respectively. PTPS-I of 400 μg/mL significantly reduced malondialdehyde (MDA) content to 1.31 ± 0.288 μmol/mg prot and inhibited the decline of mitochondrial membrane potential (MMP) by 9.67%. The three polysaccharide fractions could elevate the mRNA expression of Nrf2, NQO1 and HO-1 in the Nrf2/HO-1 signaling pathway and the gene expression of PPARα, CPT-1 and ACOX1 in the lipid metabolism pathway, and ultimately regulate lipid accumulation in L02 cells. This study validated the in vitro antilipid activities of partridge tea leaves polysaccharide and provided fundamental data for research on its bioactivity and functional components. Further in vivo assays and mechanism exploration will be conducted to evaluate its potential application in fatty liver intervention product development. Full article