Search Results (748)

Tacrolimus (TAC)-induced chronic nephrotoxicity (TAC nephrotoxicity) remains a major contributor to late allograft dysfunction in kidney transplant recipients. Although detailed mechanisms remain incompletely understood, our previous metabolomic studies revealed disruptions in carnitine-related and redox pathways, suggesting impaired mitochondrial β-oxidation of fatty acids. To further characterize metabolic alterations associated with this condition, we conducted an untargeted lipidomic analysis of renal tissues using a murine model of TAC nephrotoxicity. TAC (1 mg/kg/day) or saline was subcutaneously administered to male ICR mice for 28 days, and kidney tissues were harvested for comprehensive lipidomic profiling. Lipidomic analysis was performed with liquid chromatography–tandem mass spectrometry (p < 0.05, n = 5/group). Triacylglycerols (TGs) were the predominant lipid class identified. TAC-treated mice exhibited reduced levels of unsaturated TG species with low carbon numbers, whereas TGs with higher carbon numbers and various degrees of unsaturation were increased. All detected TGs containing docosahexaenoic acid (DHA) showed an increasing trend in TAC-treated kidneys. Although accumulation of polyunsaturated TGs has been previously observed in chronic kidney disease, the preferential increase in DHA-containing TGs appears to be a unique feature of TAC-induced nephrotoxicity. These results suggest that DHA-enriched TGs may serve as a metabolic signature of TAC nephrotoxicity and offer new insights into its pathophysiology. Full article

Background/Objectives: This is the first study to examine age-related patterns of meniscal/chondral lesions in women undergoing first-time knee arthroscopy. Methods: We analyzed meniscal tear type/location and evaluated cartilage damage in femoral condyles and the tibial plateau in a medium-sized Romanian cohort (n = 241). Results: Age was associated significantly (p ≤ 0.004) with medial meniscal damage (O.R. = 1.04, 95% CI: 1.01–1.06), medial femoral condyle chondropathy (O.R. = 1.06, 95% CI: 1.03–1.10), and medial tibial plateau chondropathy (O.R. = 1.07, 95% CI: 1.02–1.12). Medial meniscus tear patterns differed significantly between age groups (p < 0.001, Cramér’s V = 0.32). Bucket-handle tears—the most common tear type—peaked in middle age (p < 0.001, Cramér’s V = 0.30). The two menisci showed different distributions of tear patterns in women aged ≥40 years (p ≤ 0.023, Cramér’s V ≤ 0.41). Meniscal tears most commonly involved the posterior third. The distribution of tear sites in menisci (medial vs. lateral) varied significantly in women aged 40–59 years (p = 0.020, Cramér’s V = 0.28). The medial femoral condyle and medial tibial plateau showed significant intergroup differences in ICRS scores (p ≤ 0.024, Cramér’s V ≤ 0.34). The frequency of ICRS grade 4 cartilage lesions increased markedly in the 40–59 age group at both sites, continuing to rise in older patients for the medial tibial plateau. Conclusions: Knee pathology in women worsens with age, especially in the medial compartment. Early screening (intervention) in middle-aged women may help prevent advanced joint damage. Full article

Cannabis vaping, particularly involving cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), rapidly delivers highly concentrated cannabinoids to the brain, potentially affecting the hippocampus. This study examined differential expression of long noncoding RNAs (lncRNAs) and mRNAs in the hippocampus after acute exposure to vaporized CBD or THC. Male ICR mice were exposed to vaporized CBD or THC (50 mg, n = 5/group), and hippocampal tissues were collected at 1, 3, and 14 days post-exposure. Total RNA sequencing was conducted on day 1 samples, and selected transcripts were validated using qRT-PCR across multiple time points. CBD led to significant up- or downregulation of L3mbtl1, Wnt7a, and Camk2b at day 1. However, Wnt7a showed gradual recovery at days 3 and 14. In the THC group, Grin2a, Gria3, and Golga2 were significantly upregulated, while Drd1, Drd2, Gnal, and Adcy5 were significantly downregulated at day 1. Time-course analysis showed that Drd2 expression returned to baseline by day 14, whereas Adcy5 remained persistently downregulated through days 3 and 14. In the CBD group, NONMMUT069014.2 was upregulated, while NONMMUT033147.2 and NONMMUT072606.2 were downregulated at day 1; notably, NONMMUT072606.2 showed a transient increase at day 3 before returning to baseline. In the THC group, NONMMUT085523.1 and NONMMUT123548.1 were upregulated, whereas NONMMUT019734.2, NONMMUT057101.2, and NONMMUT004928.2 were downregulated, with most showing gradual recovery by day 14. Correlation analysis revealed that THC-responsive lncRNAs—including NONMMUT004928.2, NONMMUT057101.2, and NONMMUT019734.2—were strongly associated with downregulated mRNAs such as Drd2 and Adcy5. These findings highlight cannabinoid-specific hippocampal transcriptomic responses and suggest potential regulatory roles for lncRNA–mRNA interactions in cannabinoid-induced neural changes. Full article

Retinal degeneration is associated with dietary factors and environmental light exposure. This study investigated the effects of a high-fructose high-fat (HFHF) diet on susceptibility to blue light (BL)-induced retinal damage. Male ICR mice were randomized into three groups: control, BL alone, and BL plus HFHF diet (BL + HFHF). The BL + HFHF group consumed the HFHF diet for 40 weeks, followed by 8 weeks of low-intensity BL exposure (465 nm, 37.7 lux, 0.8 μW/cm²) for 6 h daily. The BL group underwent the same BL exposure while kept on a standard diet. Histopathological analysis showed that, under BL exposure, the HFHF diet significantly reduced the number of photoreceptor nuclei and the thickness of the outer nuclear layer and inner/outer segments compared to the BL group (p < 0.05). While BL exposure alone caused oxidative DNA damage, rhodopsin loss, and Müller cell activation, the combination with an HFHF diet significantly amplified the oxidative DNA damage and Müller cell activation. Moreover, the HFHF diet increased blood–retinal barrier permeability and triggered apoptosis under BL exposure. Mechanistically, the BL + HFHF group exhibited increased retinal advanced glycated end product (AGE) deposition, accompanied by the activation of the receptor for AGE (RAGE), NFκB, and the NLRP3 inflammasome-dependent IL-1β pathway. In conclusion, this study underscores that unhealthy dietary factors, particularly those high in fructose and fat, may intensify the hazard of BL and adversely impact visual health. Full article

Purpose: Pellucid Marginal Degeneration (PMD) is a rare ectatic corneal disorder characterized by inferior peripheral thinning and significant irregular astigmatism. Despite its clinical similarities to keratoconus, PMD presents unique diagnostic and therapeutic challenges. This review aims to provide a comprehensive update on the pathophysiology, clinical features, diagnostic approaches, and management strategies for PMD, emphasizing the latest advancements in treatment options. Methods: A systematic literature search was performed in MEDLINE (via PubMed), Google Scholar, and Scopus up to February 2025 using the terms: “pellucid marginal degeneration,” “PMD,” “ectatic corneal disorders,” “keratoplasty in PMD,” “corneal cross-linking in PMD,” “ICRS in PMD,” “toric IOL PMD” and their Boolean combinations (AND/OR). The search was restricted to English-language studies involving human subjects, including case reports, case series, retrospective studies, clinical trials, and systematic reviews. A total of 76 studies met the inclusion criteria addressing treatment outcomes in PMD. Results: PMD is characterized by a crescent-shaped band of inferior corneal thinning, leading to high irregular astigmatism and reduced visual acuity. Diagnosis relies on advanced imaging techniques such as Scheimpflug-based corneal tomography, which reveals the characteristic “crab-claw” pattern. Conservative management includes rigid gas-permeable (RGP) lenses and scleral lenses, which provide effective visual rehabilitation in mild to moderate cases. Surgical options, such as CXL, ICRS, and toric IOLs, are reserved for advanced cases, with varying degrees of success. Newer techniques such as CAIRS, employing donor tissue instead of synthetic rings, show promising outcomes in corneal remodeling with potentially improved biocompatibility. Penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK) remain definitive treatments for severe PMD, though they are associated with significant risks, including graft rejection and postoperative astigmatism. Conclusions: PMD is a complex and progressive corneal disorder that requires a tailored approach to management. Early diagnosis and intervention are critical to optimizing visual outcomes. While conservative measures are effective in mild cases, surgical interventions offer promising results for advanced disease. Further research is needed to refine treatment protocols and improve long-term outcomes for patients with PMD. Full article

The aim of this study was to compare IC and CSR and to examine ICr as a mediating variable. The study employed a relational survey design and involved participants drawn from industrial organizations based in Tehran. To evaluate participants’ perceptions of innovation climate, corporate social responsibility, and Individual Creativity, standardized questionnaires were used. In analyzing the findings, the structural equation modeling (SEM) approach was adopted, and the analyses were conducted using SPSS AMOS version 26. The analysis revealed that an Innovative Climate exerts a positive and statistically significant influence on CSR. In addition, a positive and significant association was identified between Innovative Climate and Individual Creativity. The results further demonstrated a meaningful relationship between Individual Creativity and CSR. Finally, to test the hypothesis of partial mediation, the study confirmed that Individual Creativity functions as a mediating mechanism between IC and CSR. Overall, these findings highlight the critical role of an innovative environment in enhancing CSR efforts from the perspective of Individual Creativity, and they provide insight for future studies aimed at developing strategies to strengthen creativity as a strategic means of achieving more effective CSR outcomes. The study advocates the development of an innovation-oriented mindset as a pathway to promoting socially responsible practices within Tehran’s industrial sector. Full article

Background: Constipation is a common gastrointestinal disorder with a significant impact on quality of life. Methods: Constipation was induced in male ICR mice via 25% cotrimoxazole gavage (20 mL/kg/day for 7 days). Mice were divided into prevention (pre-MBSFL), treatment (MBSFL), and control groups. MBSFL was prepared by fermenting mung bean starch with Lactobacillus plantarum (1:3 w/v ratio, 37 °C for 48 h), and administered via daily oral gavage (250 mg/kg bw) for 14 days. Fecal parameters (water content and first black stool latency), gastrointestinal motility (gastric emptying and small intestinal propulsion), serum biomarkers (NO, VIP, SP, and 5-HT), and intestinal gene expression (5HTR₄, SERT, and MAO_A) were analyzed. Results: MBSFL intervention restored fecal water content by 38%, reduced first black stool latency from 6.2 h to 3.1 h, and improved small intestinal propulsion by 64%. Additionally, it downregulated serum NO (25%) and VIP (32%) while upregulating SP (49%) and 5-HT (78%) levels. Intestinal 5HTR4 and SERT expression increased by 78% and 71%, respectively, with MAOA suppression (25%). Microbial analysis revealed a 140% increase in Dubosiella and 49% in Lactobacillus abundance, alongside a 62% reduction in Mucispirillum. MBSFL contained polysaccharides (12.3% w/w) and organic acids, including hydroxy butyric acid (4.2 mg/mL). Conclusions: MBSFL alleviates constipation through dual mechanisms: modulating 5-HT pathway activity and restoring gut microbiota homeostasis. Full article

Swine wastewater (SW) has a high chemical oxygen demand (COD) content and is difficult to degrade; an effective strategy to address this issue is through biodegradation, which poses negligible secondary pollution risks and ensures cost-efficiency. The objectives of this study were to isolate an effective COD-degrading strain of SW, characterize (at the molecular level) its transformation of SW, and apply it to practical production. A strain of Corynebacterium xerosis H1 was isolated and had a 27.93% ± 0.68% (mean ± SD) degradation rate of COD in SW. This strain precipitated growth in liquids, which has the advantage of not needing to be immobilized, unlike other wastewater-degrading bacteria. Based on analysis by Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS), this bacterium removed nitrogen-containing compounds in SW, with proteins and lipids decreasing from 41 to 10% and lignins increasing from 51 to 82%. Furthermore, the enhancement of the sequencing batch reactor (SBR) with strain H1 improved COD removal in effluent, with reductions in the fluorescence intensity of aromatic protein I, aromatic protein II, humic-like acids, and fulvic acid regions. In addition, based on 16S rRNA gene sequencing analysis, SBR_H1 successfully colonized some H1 bacteria and had a higher abundance of functional microbiota than SBR_C. This study confirms that Corynebacterium xerosis H1, as a carrier-free efficient strain, can be directly applied to swine wastewater treatment, reducing carrier costs and the risk of secondary pollution. The discovery of this strain enriches the microbial resource pool for SW COD degradation and provides a new scheme with both economic and environmental friendliness for large-scale treatment. Full article

The motion control of a tracked mobile robot remains an important capability for autonomous navigation. Kinematic path-tracking algorithms are commonly used in mobile robotics due to their ease of implementation and real-time computational cost advantage. This paper integrates an extended Kalman filter (EKF) into a common kinematic controller for path-tracking performance improvement. The extended Kalman filter estimates the instantaneous center of rotation (ICR) of tracks using the sensor readings of GPS and IMU. These ICR estimations are then given as input to the motion control algorithm to generate the track velocity demands. The platform to be controlled is a heavyweight off-road tracked vehicle, which necessitates the investigation of slip values. A high-fidelity simulation model, which is verified with field tests, is used as the plant in the path-tracking simulations. The performance of the filter and the algorithm is also demonstrated in field tests on a stabilized road. The field results show that the proposed estimation increases the path-tracking accuracy significantly (about 44%) compared to the classical pure pursuit. Full article

Astrocytes, which proliferate after brain injury, represent a promising target for cellular reprogramming due to their abundance and ability to support brain repair. In this study, we investigated the in vitro reprogramming of primary cortical astrocytes from neonatal rats into neuronal precursor cells (NPCs) using the transcription factors Oct4, Sox2, and Klf4 (OSK), delivered via lentiviral vectors. We designed a reporter system to trace the conversion of astrocytes to NPCs and neurons by using GFAP-driven iCre and Nestin- or Synapsin1-driven fluorescent reporters. After transduction, we observed morphological changes and the expression of neuronal markers in some cells, while many cells remained in a transitional state, expressing both astrocytic and neuronal features. Importantly, the study was not designed to quantify reprogramming efficiency or demonstrate full astrocyte-to-neuron conversion but rather to establish and evaluate a traceable reporter system. Our data suggest that OSK-mediated reprogramming in this in vitro model can initiate conversion of astrocytes to neuronal precursor-like cells, although the process is complex and incomplete within the one-week timeframe. We also highlight limitations in co-transduction efficiency and potential silencing of the reporter system during reprogramming. These findings provide an initial technical platform to explore astrocyte reprogramming in vitro and inform future studies aiming to refine these methods and apply them in vivo. Full article

Scoring functions are key elements in docking protocols as they approximate the binding affinity of a ligand (usually a small bioactive molecule) by calculating its interaction energy with a biomacromolecule (usually a protein). In this study, we present a pairwise comparison of scoring functions applying a multi-criterion decision-making approach based on InterCriteria analysis (ICrA). As criteria, the five scoring functions implemented in MOE (Molecular Operating Environment) software were selected, and their performance on a set of protein–ligand complexes from the PDBbind database was compared. The following docking outputs were used: the best docking score, the lowest root mean square deviation (RMSD) between the predicted poses and the co-crystallized ligand, the RMSD between the best docking score pose and the co-crystallized ligand, and the docking score of the pose with the lowest RMSD to the co-crystallized ligand. The impact of ICrA thresholds on the relations between the scoring functions was investigated. A correlation analysis was also performed and juxtaposed with the ICrA. Our results reveal the lowest RMSD as the best-performing docking output and two scoring functions (Alpha HB and London dG) as having the highest comparability. The proposed approach can be applied to any other scoring functions and protein–ligand complexes of interest. Full article

Cyclic hydraulic loading frequently affects embankment dams during reservoir regulation, tidal fluctuations, and intense rainfall. It potentially worsens fine particle migration during internal erosion and increases dam failure risks. This study is the first to systematically explore the influence of cyclic hydraulic loading on the critical hydraulic gradient (i_cr) of gap-graded soils, providing new insights into suffusion behavior. Transparent soil experiments, which enable direct observation of soil structural evolution, are combined with coupled DEM–Darcy simulations that offer microscopic mechanical insights, marking the first integrated use of these two approaches to investigate suffusion behavior. To quantify fine particle migration, we propose a novel modified grayscale threshold segmentation (MGTS) method for analyzing cross-sectional images captured during transparent soil experiments. The results from both methods show consistency in fine particle migration, clogging formation, and failure, with differences in permeability and i_cr remaining within acceptable limits. Fine particle content significantly influences the post-cyclic i_cr of internally unstable soils. For soils with lower fine particle content (15%), i_cr increases after cyclic hydraulic loading and rises with the mean hydraulic gradient during cycling. Conversely, soils with higher fine particle content (20%) exhibit a decrease in post-cyclic i_cr. This behavior is explained by changes in the average contact force between fine particles (F_ff) observed in DEM simulations. Full article

In the methylation of pseudocumene with methanol over IM-5 zeolite, the yield of durene can be enhanced. However, poorer stability of the catalytic activity was observed, especially at a higher methanol/pseudocumene ratio. In this paper, conventional characterization methods (XRD, XRF, TGA, SEM, physical adsorption, OH-IR, NH₃-TPD, and Py-IR) were used to characterize fresh and deactivated IM-5 zeolite and ZSM-5. FT-IR, XPS, TG-MS, GC-MS, FT-ICR MS, and NMR were employed to characterize deactivated IM-5 zeolite. It was found that the deactivation of IM-5 zeolite was mainly due to the severe coverage of acidic sites and pore channels by carbon deposits. The carbon deposits within the internal surface had a higher abundance, mainly in the form of linear unsaturated chain-like structures with a high degree of unsaturation. The carbon deposits on the external surface were mainly polycyclic aromatic hydrocarbons with alkyl side chains and a high degree of saturation, accompanied by unreacted methanol. Moreover, graphitized carbon existed on both the internal and external surfaces, which made the conventional coke-burning regeneration method unable to restore the activity of the post-reaction IM-5 zeolite. This work had certain reference significance for modulating the acidity and pore channels of zeolite catalysts, thus improving the activity and stability of the catalysts and extending their service life. Full article

Background/Objectives: Allergens can trigger severe immune responses in hypersensitive individuals, with mast cells releasing inflammatory mediators via IgE-FcɛRI signaling. Spleen tyrosine kinase (Syk) is a key regulator in this pathway, making it a promising therapeutic target. Natural modulators of Syk-mediated mast cell activation remain underexplored. This study investigated the anti-allergic effects of a 70% ethanol extract of Salvia miltiorrhiza (SME) using in vitro and in vivo models. Methods: SME was evaluated using IgE-sensitized RBL-2H3 cells, a passive cutaneous anaphylaxis model, and a DNCB-induced atopic dermatitis-like mouse model. Allergic responses were assessed via degranulation assays, histopathology, serum IgE levels, and the spleen index. Results: SME significantly inhibited mast cell degranulation by 44.4 ± 1.6% in RBL-2H3 cells at 100 µg/mL following 30 min of treatment compared to the untreated control. Western blot analysis demonstrated dose-dependent suppression of protein kinase B (PKB, also known as AKT), c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and spleen tyrosine kinase (Syk) phosphorylation, indicating inhibition of key allergic signaling pathways. In an IgE/Ag-induced passive cutaneous anaphylaxis model in ICR mice, SME (100 mg/kg, orally) significantly attenuated vascular permeability, as evidenced by a 20.6 ± 9.7% reduction in Evans blue extravasation relative to the Ag-treated group. In a 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD)-like model, six treatments of SME significantly improved the skin condition, reduced spleen enlargement associated with allergic inflammation, and decreased serum IgE levels by 43.3 ± 11.2% compared to the DNCB group. Conclusions: These findings suggest that SME may help to alleviate allergic responses and AD by modulating key immune signaling pathways. Full article

Casein Kinase II (CK2) is a ubiquitously present serine/threonine kinase essential for mammalian development. CK2 holoenzyme is a tetramer with two highly related catalytic subunits (α or α’) and two regulatory ß subunits. Global deletion of the α or β subunit in mice is embryonically lethal. We and others have shown that CK2 is overexpressed in leukemia cells and plays an important role in cell cycle, survival, and resistance to the apoptosis of leukemia stem cells (LSCs). To study the role of CK2α in adult mouse hematopoiesis, we generated hematopoietic cell-specific CK2α-conditional knockout mice (Vav-iCreCK2 ^f/f). Here we report the generation and validation of a novel mouse model that lacks CK2α in the hematopoietic compartment. Vav-iCreCK2α ^f/f mice were viable without dysmorphic features and showed a mild phenotype under baseline conditions. In Vav-iCreCK2α ^f/f mice, the blood count showed a significant decrease in total red blood cells and platelets. The spleen was enlarged in Vav-iCreCK2α ^f/f mice with evidence of extramedullary hematopoiesis. HSC and early progenitor cell compartments showed expansion in CK2α-null bone marrow, suggesting that the absence of CK2α impaired their proliferation and differentiation. Given the established roles of CK2 in cell cycle regulation and the findings reported here, further functional studies are warranted to investigate the role of CK2α in HSC self-renewal and differentiation. This mouse model serves as a valuable tool for understanding the role of CK2α in normal and malignant hematopoiesis. Full article