Search Results (60,995)

Objective: While Sanzi Sijun Formula (SSF) has exhibited preliminary efficacy against metabolic dysfunction-associated steatotic liver disease (MASLD), its mode of action remains undefined. This study therefore aimed to unravel its core therapeutic mechanisms. Methods: UPLC-MS was employed to characterize the major components of SSF. Male C57BL/6J mice were fed a high-fat diet combined with high-fructose/glucose drinking water (HFD-HF/G) for 10 weeks to establish a MASLD model, followed by SSF intervention. After 8-week treatment, body and liver weight, hepatic histopathological alterations, serum levels of lipids, transaminase, and inflammatory cytokines were detected, and transcriptomic sequencing was performed on mouse liver tissues for mechanistic exploration. AML12 hepatocytes stimulated with palmitic acid (PA) were treated with SSF alone or in combination with AMPK or SIRT1 specific inhibitors. RT-qPCR and Western blotting were used to detect the expression or activation levels of AMPK, SIRT1, and key lipid metabolism-related molecules. Results: A total of 77 active components were identified in SSF by UPLC-MS analysis. In MASLD model mice, SSF significantly reduced body and liver weight, serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and alanine aminotransferase (ALT), suppressed the pro-inflammatory cytokines including TNF-α and IL-6, and elevated adiponectin levels. Histopathological staining demonstrated that SSF effectively alleviated hepatic steatosis, ballooning, and inflammatory cell infiltration. Transcriptomic profiling analysis verified the major regulatory effect of SSF on lipid metabolism and identified the AMPK/SIRT1 signaling pathway as a potential mechanism. Further experiments confirmed that SSF restored the levels of AMPK/ACC phosphorylation and SIRT1 expression, thereby modulating downstream lipid metabolism-related genes in liver tissues. In PA-induced AML12 cells, SSF significantly reduced intracellular accumulation of lipid and reactive oxygen species (ROS), which were partially abrogated by the inhibitors of AMPK or SIRT1. Conclusions: SSF exerts prominent effects against MASLD in both in vivo and in vitro models. Modulation of the AMPK/SIRT1 signaling pathway primarily contributes to its therapeutic mechanism against lipid metabolism disorder and lipotoxic liver injury. These findings provide experimental evidence to support the clinical application of SSF for MASLD treatment. Full article

Diatoms are microscopic algae with silica walls; they evolved relatively recently compared to other algal groups but have the greatest diversity of any and are abundant enough to contribute a fifth of the oxygen in the atmosphere and to have accumulated fossil mineral deposits (diatomaceous earth). Among the most recent and most diverse diatom genera is Mastogloia, with over 370 valid taxa but so far no pattern of phylogenetic relationships among the species. The genus is defined by the presence of chambers (partecta) on the girdle bands, which are as varied as the valve shapes and pore patterns. Mastogloia decussata was described in 1892, but its structure is still poorly understood, including whether it has axial costae and the nature of a V-shaped structure reported in 1970. A similar species, M. singaporensis, differs in having narrower, quadrate partecta that occupy only the middle half of the band; it has axial costae. We have observed several populations with quadrate partecta extending nearly to the apices in samples from Micronesian and Caribbean islands; such specimens have also been reported in the literature misidentified as M. decussata. The objective was to establish the ultrastructure of these species. Four major findings are as follows: (1) We establish the correct description of M. decussata with a neotype and show that it has axial costae; (2) we show that it has compound partecta with intrapartectal cylinders; (3) we describe one new species, M. paddocketkempii Lobban & J.A.B.Valencia, which also has compound partecta; (4) we show that all have dual pseudoloculate valve walls with interior and exterior pseudoloculi in slightly offset hexagonal arrays. The new species occurred in both ocean basins and may include simulacra, but we could not separate them morphologically. Detailed SEM of M. singaporensis shows its structural similarity to the other two species. Full article

Mitochondrial diseases are a heterogeneous group of inherited disorders caused by defects in the mitochondrial genome or nuclear genes encoding proteins essential for mitochondrial function. These conditions are characterised by progressive dysfunction of tissues with high energy demands, particularly the nervous and muscular systems. In recent years, increasing consideration has been paid to the role of autophagy—the cellular mechanism for the degradation and recycling of intracellular components in the pathogenesis of mitochondrial diseases. This review synthesizes current knowledge on molecular mechanisms of macroautophagy and selective forms of au-tophagy targeting specific organelles and structures: mitophagy, pexophagy, ribophagy, ER-phagy, aggrephagy, lipophagy, lisophagy, and nucleophagy. Using classic mitochondrial syndromes—Kearns–Sayre syndrome (KSS), MERRF, and MELAS, as well as various mitochondrial myopathies—as examples, we discuss experimental evidence indicating both compensatory activation of autophagy and its insufficiency or blockade at different stages. Furthermore, we examine the link between deficiencies of key fatty acid β-oxidation enzymes (VLCAD, MCAD, CPT2) and impaired autophagic flux, including secondary defects of mitophagy mediated by energy deficiency. The review systematises current understanding of how dysregulation of selective autophagy promotes the accumulation of damaged mitochondria, oxidative stress, inflammation, and cell death in mitochondrial diseases. Prospects for therapeutic modulation of autophagy as a potential approach to treating these disorders are discussed. Full article

Sorghum seeds accumulate substantial amounts of condensed tannins (CTs), which are also referred to as proanthocyanidins (PAs), contributing to their characteristic astringent taste. Flavan-3-ol polymers, known as PAs, are sequestered within plant vacuoles and become catalytically activated via laccase enzymes. However, the biological roles and regulatory pathways of laccases in sorghum are still largely unclear. Here, integrated transcriptomic and metabolomic profiling of developing sorghum seeds identified 7942 differentially expressed genes between low- and high-CT lines, with Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment revealing flavonoid biosynthesis as a key pathway; weighted gene co-expression network analysis (WGCNA) further pinpointed SbLAC14 as a hub gene within the module most strongly correlated with CT content. We then examined its regulation by microRNA397 (SbmiR397-5p). Dual-luciferase assays confirmed the binding of SbmiR397-5p to SbLAC14 in co-transformed tobacco leaves. Overexpressing SbLAC14 in transgenic Arabidopsis significantly increased CT accumulation while decreasing catechin and epicatechin levels. Furthermore, transgenic plants overexpressing miR397 (OEmiR397-5p) exhibited reduced CT content, accompanied by a lightening of seed color. Conversely, transgenic lines overexpressing a miR397-insensitive laccase transcript exhibited a reversed phenotypic outcome. Our findings indicate that SbmiR397-5p negatively regulates the expression of SbLAC14 in relation to CT biosynthesis, identifying it as a potential target for manipulating CT metabolism in sorghum. Those results provide a genetic entry point for metabolic engineering and breeding efforts aimed at modulating grain phenolic profiles. Full article

Understanding whether long-term vascular cambium vitality in ancient trees reflects progressive decline or adaptive reprogramming is central to grasping woody plant longevity. We performed an integrative analysis of functional traits, transcriptome profiles, and metabolomic landscapes of cambial zone enriched from 80-, 500-, and 1000-year-old Styphnolobium japonicum trees. With increasing tree age, the vascular cambium showed fewer cell layers, reduced thickness, and lower auxin, gibberellin, and IAA/ABA ratios, whereas bark thickness, malondialdehyde, abscisic acid, jasmonic acid, and salicylic acid contents increased. Transcriptomic and metabolomic analyses revealed that differentially expressed genes and metabolites were primarily enriched in the cell cycle, phytohormone signaling, and phenylpropanoid biosynthesis pathways. Specifically, genes associated with cell division were down-regulated in millennial trees, whereas phenolic acids, flavonoids, and lignin-related metabolites significantly accumulated. Piecewise structural equation modeling suggested associations among tree age, transcription factors, structural genes, metabolites, and cambial functional traits. These results indicate that cambial senescence is not a simple linear decay but a highly coordinated remodeling process, providing crucial evidence for delayed senescence in long-lived woody species. Full article

The paradigm of sustainable development, coupled with contemporary inclinations towards green construction, exerts a considerable effect on the evolution of environmentally benign building composites. The main aim of this study is to create geopolymer composites with improved physical and mechanical properties. An examination of the properties of a geopolymer composite (GS), using ground granulated blast furnace slag (GGBFS) and plant fibers, is presented in this paper. Sisal (SF) and flax (FF) fibers, along with their combination (SF + FF), were integrated into the slag at concentrations of 0%, 0.5%, 1.0%, 1.5%, and 2% by weight. Before use, plant fibers were treated with a 5% NaOH solution. The geopolymer composites (GC) underwent evaluation for their density, compressive and flexural strengths, and water absorption characteristics. Scanning electron microscopy was employed to examine the fracture characteristics of the GC. The compressive and flexural strengths of GC were improved by including 1% SF, FF, and their combination, 0.5% SF + 0.5% FF. Compressive strength increases were 11.5%, 8.6%, and 14.5%, while flexural strength increases were 17.4%, 13%, and 19.6%, respectively. Water absorption of GC with 1% SF, FF, and SF + FF decreased by 14.6%, 10.8%, and 20.4%, respectively. The apparent synergistic performance of hybrid sisal-flax reinforcement at a total fiber content of 1% was revealed. GCs at the fracture have a homogeneous rough structure with microcracks and accumulations of geopolymer reaction products. The matrix-plant fiber interface in GC is identified by a rounded region with elongated fibers, indicating the fiber’s performance under mechanical stress. The findings of this investigation suggest the feasibility of utilizing plant fibers in environmentally sound geopolymer construction composites. Full article

Background/Objectives: Hydrogen gas (H₂) inhalation has shown neuroprotective effects in neonatal hypoxic–ischemic models. However, its impact on pulmonary endothelial activation and respiratory function after hypoxic–ischemic insult remains unclear. This study investigated whether H₂ inhalation augments pulmonary endothelial activation or impairs pulmonary function during the acute phase after neonatal hypoxic–ischemic injury. Methods: Sixteen newborn Camborough^® piglets within 24 h of birth were subjected to hypoxic–ischemic insult and randomized to an untreated group (HI, n = 8) or an H₂-treated group (HI-H₂, n = 8). The HI-H₂ group received 2.1–2.7% H₂ for 6 h. Pulmonary ICAM-1 and inducible nitric oxide synthase (iNOS) expression were assessed by immunofluorescence, lung neutrophils were quantified histologically, and pulmonary function was evaluated using arterial blood gases, oxygen index, and alveolar–arterial oxygen difference. The relationship between lung neutrophil counts and right ventricular cardiac output was also examined. Results: H₂ inhalation did not increase pulmonary ICAM-1 expression or iNOS induction compared with untreated animals. Although lung neutrophil counts were significantly higher in the HI-H₂ group, pulmonary gas exchange remained preserved, with no significant differences in arterial blood gases, oxygen index, or alveolar–arterial oxygen difference. Lung neutrophil counts were positively correlated with right ventricular cardiac output, suggesting that enhanced pulmonary perfusion may contribute to neutrophil redistribution rather than inflammatory recruitment. Conclusions: H₂ inhalation preserved pulmonary endothelial homeostasis without impairing respiratory function during the acute phase after neonatal hypoxic–ischemic insult. The observed increase in lung neutrophils was not accompanied by evidence of endothelial activation or deterioration of gas exchange, supporting the acute pulmonary safety of H₂ inhalation while suggesting that neutrophil accumulation may, at least in part, reflect hemodynamic redistribution rather than injurious inflammatory infiltration. Full article

In response to common issues with traditional automotive switches, such as poor contact of terminals, low durability, and weak vibration resistance, this paper proposes and designs a novel high-performance automotive toggle switch. Through structural design and parameter optimization, a new solution is provided to enhance the structural strength and service life of automotive electronic components. After completing three-dimensional modeling based on SolidWorks 2025, a full set of simulation analyses was carried out using ANSYS Workbench 2024 R2. After structural optimization, the maximum stress of the core valve stem decreased from 17.19 MPa to 14.877 MPa, a reduction of 13.5%; meanwhile, the fatigue life increased to 2.51 times that before optimization, indicating that for polycarbonate materials, a slight reduction in stress can significantly slow the rate of component damage accumulation. The switch’s first-order natural frequency is 1171.7 Hz, and a random vibration analysis of the switch was conducted according to the industry standard ISO 16750-3:2023. Under excitations covering the entire 2000 Hz frequency range, the switch structure did not show deformation or fatigue risks caused by resonance, indirectly confirming that vibration energy density is often more concentrated at low frequencies. This study not only completes the innovative design and performance verification of the novel toggle switch but also demonstrates that the comprehensive research methods employed provide a systematic analytical approach for developing high-performance, highly reliable automotive electronic components under stringent industry standards. Full article

Internal and external stress exerted by forces such as oxidative, xenobiotic, radiant, ischemic, mechanical, metabolic, neurohormonal, infectious, immunoinflammatory, emotional and psychological increases the risk of cardiovascular morbidity and mortality. Initiation and propagation of the explosive self-amplifying chain reaction of lipid peroxidation chain reaction (LPO) generates atherogenic and inflammatory toxic reactive oxygen species that cause cardiovascular tissue lesion that are the ultimate determinants of cardiovascular disease risk (CVD-R). Because the LPO toxins, cellular stress sensors and defenses, inter- and intracellular signaling, and pathogenic lesions are closely similar among these stressors, simultaneous exposure to multiple stresses can amplify LPO to accelerate accumulation of pathogenic lesions synergistically. Numerous blood tests measure LPO-derived toxins, stress-responsive metabolism and cytokines, which are used clinically as surrogate biomarkers of CVD-R. They can predict population risks quite well, but prediction of individual patient CVD-R using multiplex biomarker panels is hampered by lack of true independence between biomarkers, lack of understanding of their relative hierarchy in disease etiology or progression, and interference from comorbid diseases or acute-phase reactions. We present this historical review of landmark studies that led to the current clinical paradigms of CVD-R prediction to provide mechanistic and clinical context that will aid the development of integrated etiological biomarkers that reflect the multiple types of stress that promote CVD-R. Full article

Abandoned paddy wetlands (APWs) develop after rice cultivation ceases and may support carbon sequestration, soil conservation, and sustainable management of abandoned agricultural land. This study quantified soil and biomass carbon in six reference APWs in the central region of the Republic of Korea. Following the Intergovernmental Panel on Climate Change (IPCC) Good Practice Guidance for Land Use, Land Use Change and Forestry (GPG-LULUCF), soil samples were collected to a depth of 30 cm to estimate soil organic matter (OM), soil organic carbon (SOC), and soil organic carbon storage per unit area (SOCS). Land cover-based carbon absorption was evaluated within 300 m hydro-ecological impact zones for 2000, 2013, and 2021, and biomass carbon was estimated for woody, herbaceous, and mixed communities using field measurements and drone LiDAR-derived vegetation structure. The mean OM and SOC contents were 33.7 and 19.54 g/kg, respectively. The corrected mean SOCS was 61.20 ± 22.28 kg/m² (unadjusted mean: 67.97 kg/m²), approximately 8.5–40 times the reference values reported for South Korean forest soils and urban parks. The mapped mean carbon absorption was 20.45 tCO₂/ha in 2000, 35.30 tCO₂/ha in 2013, and 38.14 tCO₂/ha in 2021. Because only three mapped years were analyzed, these values describe observed differences and do not establish a continuous temporal trajectory or a stable plateau. The findings suggest that APWs may contribute to sustainable land management, wetland restoration, soil conservation, and climate-change mitigation through carbon retention in soils and vegetation. These field data provide region-specific evidence for evaluating sustainable management strategies and complementing broader-scale soil–vegetation carbon models. Full article

Cotton boll opening is an important late-season indicator for maturity assessment, defoliation timing, and harvest planning, but field-level monitoring remains challenging because visible lint progression varies spatially and temporally. This study evaluates whether UAV-derived cotton visible lint percentage, aggregated at the Sentinel-2 10 m grid scale, can be estimated using Sentinel-2 spectral bands, vegetation indices (VIs), and accumulated growing degree days (AGDD) as phenological predictors. UAV multispectral imagery was used to derive visible lint percentage through red-band thresholding and segmentation within canopy masks. The UAV-derived visible lint information was summarized within fixed Sentinel-2 10 m grid cells to generate satellite-compatible response labels. Four supervised regression models, eXtreme Gradient Boosting (XGBoost), Random Forest (RF), k-Nearest Neighbors (kNN), and Neural Network/Multilayer Perceptron (NNET/MLP), were evaluated using raw and transformed target formulations. Raw visible lint percentage produced relatively high explanatory power for tree-based models, with R² values of 0.73 for both XGBoost and RF. However, the target distribution was strongly right-skewed and dominated by low visible lint values, with a mean PCTOPEN of 4.05%Open, motivating the evaluation of target transformations to reduce target skewness while assessing their impact on predictive performance. On the original PCTOPEN scale, the raw target produced RMSE = 4.38%Open points, MAE = 2.31%Open points, and MedianAE = 0.68%Open points. The square-root transformation provided the strongest overall predictive performance, maintaining R² = 0.73 and RMSE = 4.38%Open points while reducing MAE to 2.14%Open points and MedianAE to 0.41%Open points. Stronger transformations further reduced the typical prediction errors, with MedianAE = 0.35, 0.33, and 0.31%Open points for the cube-root, fourth-root, and fifth-root transformations, respectively. However, these improvements were accompanied by progressively lower R² values (0.72, 0.71, and 0.69) and higher RMSE values (4.48, 4.58, and 4.68%Open points), indicating that stronger transformations reduced typical prediction errors at the expense of overall predictive performance. These results indicate that UAV-derived visible lint percentage can be linked with Sentinel-2 observations for satellite-scale regression modeling, but prediction uncertainty remains influenced by target skewness, mixed 10 m pixels, canopy obstruction, and limited UAV acquisition density. Additional UAV–Sentinel-2-aligned acquisitions, supporting multi-field observations, and broader validation across fields, seasons, cultivars, and production environments are needed to improve robustness and support operational cotton boll-opening tracking applications. Full article

Cold-inducible RNA-binding protein (CIRP/CIRBP) is recognized as an extracellular damage-associated molecular pattern. However, its relationship to endothelial redox-inflammatory injury in atherosclerosis remains poorly characterized. Here, we explored the associations among CIRP, endothelial dysfunction, and TLR4-/SIRT6-related changes. In high-fat diet (HFD)-fed ApoE^−/− mice, circulating CIRP was elevated and positively correlated with atherosclerotic plaque burden. This increase coincided with systemic redox imbalance, impaired NO/eNOS activity, and vascular inflammation. In HUVECs, CIRP exposure reduced cell viability and impaired NO/eNOS function. These effects were accompanied by increased ROS accumulation and MDA content, together with reduced GSH-Px activity. CIRP also increased inflammatory cytokine production, NF-κB p65 phosphorylation, and THP-1 adhesion. At the molecular level, CIRP reduced SIRT6 expression. Overexpression of SIRT6 attenuated CIRP-induced endothelial injury, oxidative stress, and NO/eNOS dysfunction. CIRP also increased TLR4 expression. Accordingly, pharmacological TLR4 inhibition with TAK-242 attenuated CIRP-associated endothelial injury and partially restored SIRT6 expression and protein stability. Conversely, SIRT6 silencing weakened the protective effects of TAK-242. In addition, CIRP exposure was accompanied by increased overall eNOS acetylation. This increase was attenuated by TAK-242 and further enhanced by SIRT6 silencing. Exploratory cross-context transcriptomic analysis identified overlapping inflammatory and oxidative stress-related signatures. Representative antioxidant-related changes were further examined in CIRP-treated HUVECs through assessment of GPX4 and CAT mRNA expression and CAT activity. Finally, in a preliminary clinical cohort, serum CIRP levels were higher in patients with coronary heart disease and were positively associated with Gensini score, including selected exploratory multivariable models. Overall, these findings provide preliminary evidence that CIRP is associated with redox-inflammatory endothelial injury. The results are also consistent with the possible involvement of TLR4-/SIRT6-related signaling. These observations should be interpreted cautiously because of the relatively high CIRP concentration used in vitro, the cross-context transcriptomic comparison, and the small clinical cohort. Full article

Sea buckthorn (Hippophae rhamnoides L.), known as a “superfruit” due to its complex nutritional profile, exhibits significant variations in bioactive compounds depending on variety and ripening stage. This study evaluates the ripening dynamics of four specific varieties—Dora, Cora, Clara, and Mara—cultivated in the Republic of Moldova to identify the optimal harvest window and technological potential for each variety. Over a seven-week period (August–September), several physicochemical and biochemical parameters were monitored, including pH, titratable acidity, total soluble solids (TSS), total dry matter (TDM), lipid content, color, hardness, vitamin C, total carotenoids content (TCC), and organic acids. Analytical methods such as refractometry, spectrophotometry, and capillary electrophoresis were employed to track these components. A downward trend in TSS and titratable acidity, characteristic of non-climacteric fruits, was observed. The Cora and Mara varieties exhibited the highest productivity and total dry matter content (up to 35.61%), making them suitable for concentrated food products. Clara stood out with the highest lipid accumulation (reaching 2.32%), identifying it as the premium variety for oil extraction. Vitamin C levels generally decreased across all varieties during ripening, with the Mara variety maintaining the highest concentrations (up to 518 mg/100 g). Conversely, total carotenoids showed a peak during full maturity (late August) for most varieties, with Dora reaching the highest values (40.73 mg/100 g). The present study highlights that the optimal harvest time for maximizing bioactive compounds is between late August and early September. Full article

Water hyacinth (Eichhornia crassipes, WH) is a highly invasive aquatic plant. Although its surplus biomass has been proposed as an agricultural amendment, uncertainty remains regarding its safe use. Based on this knowledge gap, two working hypotheses were addressed: (i) WH application would enhance soil physicochemical and enzymatic attributes, particularly under water stress, and (ii) WH application would stimulate plant growth through nutrient release. To verify this, two WH amendment rates (2.5% and 5% w/w) were evaluated under normal (45%) and severe (22.5%) WHC using tomato (Solanum lycopersicum L.) as a bioindicator. WH incorporation significantly altered soil conditions, inducing progressive acidification and increasing electrical conductivity (EC), particularly at the 5% rate under well-watered conditions, where EC values reached approximately 3000 µS/cm. Although WH amendments increased soil relative humidity owing to the hydrophilic nature of the biomass, these moisture-driven benefits were transient. Acid phosphatase activity increased markedly by day 60 in WH-amended soils, especially at 45% WHC, indicating enhanced microbial activity and phosphorus mineralization associated with organic matter decomposition. Plant responses were strongly driven by water availability, with severe water restrictions consistently limiting germination and growth and potentiating osmoprotectant retention. From day 60 onward, germination and biomass declined markedly in the 5% WH treatment, likely due to the accumulation of salt and osmotic stress arising from the decomposition of biomass. Surviving seedlings in WH-amended soils exhibited increased shoot biomass relative to their roots, suggesting stress-related biomass reallocation. Overall, the results indicate that the direct application of untreated WH biomass at moderate to high rates may generate short-term benefits but may impair long-term plant establishment. Lower application rates (≤2.5% w/w) may offer limited early stage benefits, whereas higher rates pose risks under prolonged exposure, highlighting the importance of dose, water regime, and amendment processing when considering WH valorization for agricultural use. This valorization approach may contribute to incentivizing control of this invasive species while promoting plant waste valorization within circular economy goals. Full article

Bone metastasis is often treated clinically as a late complication of advanced cancer, yet accumulating evidence indicates that it is also a spatial evolutionary process shaped by clonal selection, niche adaptation, dormancy, and reseeding. This review examines BoM through a phylogeographic framework that links tumor ancestry with anatomical location and time. We discuss how heterogeneous primary tumors generate bone-tropic subclones, how circulating tumor cells pass through dissemination bottlenecks, and how disseminated tumor cells enter perivascular and endosteal niches that either maintain dormancy or support early micrometastatic outgrowth. We then compare clonal architectures across breast, prostate, lung, and renal cell carcinomas, emphasizing both lineage-specific programs and convergent bone-adaptive states, including osteomimicry, immune evasion, metabolic plasticity, and epigenetic remodeling. Methodological platforms such as multiregion sequencing, single-cell and spatial transcriptomics, lineage tracing, and liquid biopsy are evaluated with attention to the technical limitations imposed by mineralized tissue. Finally, we consider how bone lesions may function as reservoirs for secondary dissemination and how evolutionary thinking could improve biomarker development, dormancy prediction, trial design, and therapy selection. Viewing BoM as an evolving ecosystem may help shift the field from reactive skeletal management toward earlier, biology-informed intervention. Full article