Search Results (1,629)

Carbendazim (CBDZ) is widely used for the prevention and control of fungal diseases in agricultural crops. Its extensive and recurrent application may lead to the occurrence of residues in agricultural environments and increase the potential for contamination of aquatic systems. In this study, analytical diafiltration was used to investigate the transport and interfacial association of CBDZ with regenerated cellulose membranes (CELms) rather than to evaluate size-exclusion-based pesticide removal. Continuous diafiltration experiments using the washing mode were performed with an 8.0 ppm CBDZ solution and 10 kDa of CELm at different pH values (3.0–9.0), while permeate flow rate and CBDZ concentration in successive permeate fractions were monitored throughout the process. CBDZ membrane retention (R_m) ranged from (7.4 ± 3.3%) at pH 9.0 to (23.2 ± 2.0%) at pH 3.0, with a maximum membrane-associated amount (\(R_m^{max}\) ) of 478 μg CBDZ per g of CELm. The pH dependence of R_m was accurately described by R_m = 24.9740 + 0.1814 ph − 0.2375 ph² for 3.0 ≤ pH ≤ 9.0 (r² = 0.999). The results are consistent with adsorption-mediated interfacial association, mainly involving physicochemical interactions with hydroxyl- and carboxyl-containing functionalities of CELms, while electrostatic interactions contributed less than 3.0% within the pH range of 6.0–7.0. The diafiltration profiles were successfully described by the ExDM–IDZ model. The parameters governing the shape of the retention profile were R_m, associated with the horizontal asymptote, and (j), which describes the decay rate and was related to the evolution of CBDZ concentration and its apparent residence behavior during diafiltration. Overall, these results demonstrate that analytical diafiltration provides a useful framework for investigating the transport, partitioning, and adsorption-mediated interactions of low-molecular-weight, water-soluble pesticides with membrane materials. Full article

Temperature stress is a major constraint on the productivity of microalgae used in aquaculture. γ-Aminobutyric acid (GABA) is well-established as a key player in the stress tolerance of higher plants, yet its role in microalgae remains largely unexplored. Here, we examined the effects of low (15 °C), optimal (25 °C), and high (35 °C) temperatures on the GABA shunt in Isochrysis zhanjiangensis during the initial and mid-exponential growth phases. The results demonstrated that temperature stress significantly inhibited cell growth and photosynthetic efficiency (assessed by Fv/Fm and Fv’/Fm’), with soluble protein decreasing and soluble sugar accumulating. During the initial exponential phase, both low and high temperature stress triggered marked GABA accumulation, accompanied by coordinated increases in glutamate decarboxylase (GAD) and diamine oxidase (DAO) activities. Interestingly, the transcript levels of IzGAD and IzDAO decreased under these conditions, suggesting that GABA accumulation at this stage is predominantly governed by post-translational activation rather than transcriptional upregulation. Upon entry into the mid-exponential phase, a distinct phase-dependent shift in GABA biosynthetic regulation emerged. Under low temperature stress, GAD activity and IzGAD expression were both suppressed, whereas DAO activity and IzDAO transcripts increased significantly, indicating the transition to DAO-mediated GABA production as the dominant route. Under high temperature stress, both GAD and DAO activities increased, yet their corresponding gene transcription remained repressed, revealing a persistent asynchrony between enzyme activities and gene expression across both phases. Meanwhile, the expression of catabolic genes (IzGABA-T, IzSSADH1, and IzSSADH2) was consistently downregulated, further facilitating the net accumulation of GABA. Promoter analysis revealed multiple stress- and hormone-responsive cis-elements in these genes, implying a complex regulatory network. Collectively, our findings uncover a growth-phase-dependent reconfiguration of GABA biosynthetic pathways in I. zhanjiangensis under temperature stress. These insights provide a mechanistic basis for strain-specific temperature management in aquaculture applications. Full article

Continuous monocropping of tomato causes soil degradation, secondary salinization, and yield decline. Mushroom–vegetable rotation coupled with spent mushroom substrate (SMS) incorporation offers a recycling strategy to mitigate these obstacles. Here, a five-stage progressive field experiment (2023–2025, Yantai, Shandong, China) was conducted to screen the optimal local configuration of Stropharia rugosoannulata–tomato rotation and reveal its soil improvement mechanisms. The combination of variety Nieyang and an apple woodchip-based substrate achieved the highest mushroom yield, with the substrate formula (F = 11.64, p = 0.0006) dominating productivity. Deep incorporation of SMS into the 0–20 cm plow layer (M treatment) avoided the seedling stress and mortality caused by surface mulching and increased the marketable yield of the large-fruited tomato R35 by 28.0% (79,560 kg·ha⁻¹, p < 0.05) without altering fruit soluble solids (p = 0.611). Two consecutive rotation years increased soil organic carbon by 17.6% (from 3.29 to 3.87 g·kg⁻¹) and total nitrogen by 243% (from 0.79 to 2.71 g·kg⁻¹) and raised soil desalination efficiency from 33.5% to 56.2%, while soil EC and pH remained within the optimal range for tomato growth. Cross-regional verification showed universal regulation of soil pH and EC but background-dependent nutrient accumulation. The system improves soil fertility through mycelium-mediated biological desalination, progressive SMS-derived carbon pool accumulation, and complementary acid–base homeostasis, generating a net annual economic benefit of approximately 255,000 CNY·ha⁻¹ (≈38,060 USD·ha⁻¹). This recyclable rotation pattern is suitable for popularization in Jiaodong facility-grown tomato production. Full article

Vitamin E (tocopherols) is an important lipid-soluble antioxidant that contributes to plant redox homeostasis and seed longevity. To investigate relationships among BnVTE2-dependent tocopherol accumulation, antioxidant capacity, fatty acid stability, and seed storability in rapeseed, we generated Brassica napus lines overexpressing BnVTE2 (OE) and lines with RNA interference-mediated suppression of BnVTE2 (RNAi). BnVTE2 encodes homogentisate phytyltransferase, a key enzyme catalyzing the committed step in tocopherol biosynthesis. Modulation of BnVTE2 expression resulted in corresponding changes in total tocopherol content. OE lines exhibited higher superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities, lower H₂O₂ and malondialdehyde (MDA) accumulation, and improved seed performance after long-term storage, whereas RNAi lines showed the opposite trends. Transcriptome and network analyses identified lipid-related transcriptional changes and glycerolipid-associated candidate hubs; enrichments in phenylpropanoid biosynthesis and hormone signaling were treated as broader secondary responses rather than direct components of tocopherol metabolism. After 42 months of storage, seeds with higher tocopherol levels retained greater germination capacity and showed reduced lipid peroxidation relative to tocopherol-deficient lines. Together, these findings support an association among BnVTE2-mediated tocopherol accumulation, antioxidant defense, fatty acid stability, and seed longevity in B. napus. Direct validation of glycerolipid remodeling and hub-gene function will be required in future studies. Full article

Takotsubo syndrome (TTS) is an acute and reversible heart failure condition characterized by transitional left ventricular systolic dysfunction without obstructive coronary artery disease. Although sympathetic hyperactivation is considered a key pathogenic mechanism, the contribution of gut-derived endotoxemia and oxidative stress is still unclear. Lipopolysaccharide (LPS), an endotoxin of Gram-negative bacteria, may translocate from the gut into the bloodstream and increase oxidative stress through activation of NADPH oxidase 2 (NOX2), nitric oxide (NO) depletion and endothelial dysfunction. This study aimed to evaluate circulating LPS levels in TTS and investigate their association with NOX2 activation, oxidative stress, and endothelial dysfunction. Twenty consecutive patients with TTS and 20 age- and sex-matched healthy controls were included. Within 48 h of admission, fasting blood samples were collected to assess soluble NOX2-derived peptide (sNOX2-dp), hydrogen peroxide (H₂O₂), NO metabolites (NOx), LPS, and zonulin. Endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Compared with controls, TTS patients had significantly higher serum levels of sNOX2-dp, H₂O₂, LPS, and zonulin, lower NOx and impaired FMD. sNOX2-dp was positively correlated with LPS (Rs = 0.539, p < 0.001) and zonulin (Rs = 0.331, p = 0.037) and inversely correlated with FMD (Rs = −0.462, p = 0.003). NOx correlated negatively with H₂O₂, zonulin and LPS. In multivariable analysis, LPS was the only independent predictor of FMD (β = 0.498, SE = 0.126, p = 0.001) and sNOX2-dp (β = −0.572, SE = 0.034 p < 0.001); FMD (β = −0.347, SE = 0.455, p = 0.005), H₂O₂ (β = 0.445, SE = 0.155, p < 0.001), and zonulin (β = 0.298, SE = 2.309, p = 0.016) emerged as independent predictors of LPS (adjusted R² = 0.585). TTS is associated with low-grade endotoxemia, NOX2-driven oxidative stress, reduced NO bioavailability, and endothelial dysfunction. The independent association between LPS and NOX2 activation supports a potential gut–vascular axis in TTS pathophysiology. Full article

Background/Objectives: Oxidative stress, chronic inflammation, disrupted apoptosis, and altered autophagy are biological processes implicated in colorectal tumor development. Morin is a plant-derived flavonoid with antioxidant and anti-inflammatory properties, but its limited solubility and bioavailability may limit its biological activity. This study evaluated the effects of free morin and morin-loaded liposomes (MOR-Lips) on 1,2-dimethylhydrazine (DMH)-associated colonic biochemical, molecular, and histopathological alterations in rats. Methods: Rats were randomly assigned to six groups—vehicle control, MOR, MOR-Lips, DMH, DMH + MOR, and DMH + MOR-Lips—and treated for 10 weeks. Serum and colonic tissues were evaluated for cancer-associated biomarkers (CEA, CA19-9, CA125, HMG-CoA reductase), oxidative stress and antioxidant indices, nitrosative and oxidative DNA-damage markers (MDA, NO, 8-OHdG), inflammatory mediators (TLR4/NF-κB/COX-2, cytokines, MPO), proliferative indices (Ki-67, PCNA), apoptotic and autophagy-related regulators (Bax, caspase-3, p53, cytochrome c, BCL-2, p-AKT, LC3-II, Beclin-1, p62), and histopathological and immunohistochemical changes. Results: DMH exposure was associated with increased CEA, CA19-9, CA125, HMG-CoA reductase, MDA, NO, 8-OHdG, TLR4/NF-κB/COX-2, cytokines, MPO, Ki-67, and PCNA. DMH also reduced NRF2/HO-1 signaling and antioxidant defenses, shifted apoptosis-related markers toward a pro-survival profile, altered autophagy-related markers, and produced marked colonic histopathological abnormalities. Both free MOR and MOR-Lips attenuated several of these DMH-associated alterations, with MOR-Lips generally producing greater effects than free MOR. MOR-LIP treatment was associated with restoration of antioxidant marker profiles, reduced levels of inflammatory and proliferative markers, a shift toward a pro-apoptotic marker profile, partial normalization of autophagy-related markers, and improved colonic histopathological appearance. Conclusions: In DMH-exposed rats, MOR-Lips were associated with more favorable redox, inflammatory, proliferative, apoptosis-related, autophagy-related, and histopathological profiles than free MOR. These findings support further investigation of MOR-Lips as a formulation strategy for improving the biological activity of morin. Because quantitative preneoplastic and neoplastic endpoints were not measured, the results do not establish inhibition of colorectal carcinogenesis or chemopreventive efficacy. Full article

Background: Effective topical management of sensitive skin remains challenging because inadequate cutaneous delivery limits the therapeutic performance of many anti-inflammatory agents. Glycyrrhetinic acid (GA) possesses well-recognized anti-inflammatory and barrier-protective activities, yet its clinical potential is constrained by poor aqueous solubility and inefficient skin delivery. This study aimed to develop a hyaluronic acid (HA)-engineered ethosomal system to enhance the local delivery and therapeutic efficacy of GA for sensitive skin. Methods: HA-coated GA-loaded ethosomes (HAGA-ETs) were prepared by electrostatic adsorption of HA onto a cationic ethosomal template. The physicochemical properties, release behavior, storage stability, skin retention, cellular uptake, and biological activities of HAGA-ETs were systematically evaluated using TNF-α/IFN-γ-stimulated HaCaT cells and an SLS-induced 3D reconstructed skin model. Results: HAGA-ETs exhibited a mean particle size of 140.1 nm, encapsulation efficiency exceeding 95%, sustained drug release, and good storage stability. Compared with Free-GA and unmodified ethosomes, HAGA-ETs showed improved cytocompatibility, enhanced skin retention, greater keratinocyte uptake, and stronger anti-inflammatory activity. HA pre-saturation attenuated the enhanced cellular uptake of HAGA-ETs, supporting the involvement of HA receptor-mediated cellular interaction. HAGA-ETs also more effectively restored barrier-related markers, suppressed hyper-reactivity- and allergy-associated mediators, and inhibited the activation of MAPK/NF-κB, JAK1/STAT1, and TRPV1-related signaling pathways in both cellular and 3D skin models. Conclusions: HA surface engineering effectively improved the topical delivery and local therapeutic efficacy of GA by enhancing skin retention and keratinocyte interaction. HAGA-ETs represent a promising nanoplatform for the local management of sensitive skin. Full article

Gibberellins (GAs) are essential hormones that regulate plant growth and development, yet the downstream metabolic pathways through which they modulate phenotypic plasticity remain poorly understood. Here, we investigated the GA-mediated regulatory network in Agapanthus praecox subsp. orientalis by integrating phenotypic, transcriptomic, and targeted metabolomic analyses across three complementary perturbation strategies: gradient paclobutrazol (PAC) treatments, GA20ox RNA interference (RNAi) lines, and exogenous GA₄ rescue. PAC suppressed vegetative growth dose-dependently and completely arrested floral development at 200 mg·L⁻¹, while increasing soluble sugar and starch contents; plants treated with it in the first year displayed enhanced vegetative growth in the following season, suggesting a possible carbon legacy effect. GA20ox silencing caused dwarfism and flowering failure, which were largely rescued by GA₄. Exogenous GA₄ restored bioactive GA pools to above wild-type levels without recovering endogenous synthesis, indicating functional compensation. Transcriptomic and qRT-PCR analyses revealed that sugar metabolism-related genes and metabolites underwent the most pronounced changes among all tested categories; these changes were partially reversed by GA₄, though certain catabolic genes remained suppressed, revealing hierarchical regulatory logic. Collectively, these findings indicate that GA is closely associated with growth and carbohydrate allocation, and that the GA–sugar metabolic axis represents a major downstream component in developmental plasticity. This study provides species-specific insights into GA-mediated growth regulation and offers implications for ornamental crop management. Full article

Introduction: Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disorder involving ROS and ferroptosis. MXene, a 2D material, functions as both a drug carrier and ROS scavenger. Butylphthalide (NBP), a neuroprotective agent, suffers from poor aqueous solubility and bioavailability. This study synthesized Ti₂C@BSA-NBP, a novel MXene nanocomposite, to enhance NBP delivery and therapeutic efficacy for AD. Materials and Methods: Ti₂C@BSA-NBP was synthesized via self-assembly and amidation reaction, and characterized by multiple techniques. In vitro, ROS-scavenging capacity, mitochondrial function, and ferroptosis markers were assessed in H₂O₂-injured cells. In vivo efficacy was evaluated in an AD mouse model via behavioral, histopathological, and biochemical analyses. Results: The nanocomposite exhibited robust ROS-scavenging activity in vitro, significantly attenuating ROS, restoring mitochondrial function, and reversing ferroptosis markers. In vivo, Ti₂C@BSA-NBP ameliorated learning/memory deficits, partially repaired neuronal morphology, and suppressed neuroinflammation. Mechanistically, it downregulated ACSL4 and Aβ overexpression while restoring GPX4 inhibition. Discussion: Ti₂C@BSA-NBP exerts synergistic neuroprotection through MXene-mediated ROS clearance and NBP-mediated multi-target regulation, counteracting oxidative stress, ferroptosis, and neuroinflammation. Conclusions: Ti₂C@BSA-NBP is a promising multifunctional nanoplatform integrating antioxidant activity, enhanced drug delivery, and ferroptosis modulation for AD therapy. Full article

Type 2 diabetes mellitus (T2DM) remains a global health crisis, with nearly 589 million adults currently affected and projections pointing toward 853 million by 2050. Despite an expanding pharmacological armamentarium, a significant proportion of patients fail to achieve adequate glycaemic control, and the limitations of existing therapies, including adverse effects, cost, and limited accessibility, underscore the compelling need for novel therapeutic approaches. Phytochemicals such as curcumin, berberine, quercetin, resveratrol, and epigallocatechin gallate possess well-documented antidiabetic activity, operating through the PI3K/Akt, AMPK (activated protein kinase), NF-κB/JNK (nuclear factor kappa-B), and GLP-1R (glucagon-like peptide-1) signalling axes to improve insulin sensitivity, suppress gluconeogenesis, protect pancreatic beta-cells, and attenuate chronic metabolic inflammation. However, their clinical utility has been fundamentally constrained by poor oral bioavailability arising from low aqueous solubility, gastrointestinal instability, extensive first-pass metabolism, and P-glycoprotein-mediated efflux. Advanced drug delivery systems, including liposomes, solid lipid nanoparticles (SLN), nanostructured lipid carriers, PLGA (Poly (lactic-co-glycolic acid)) and chitosan nanoparticles, nanoemulsions, self-nanoemulsifying drug delivery systems, and phytosomes have demonstrated the capacity to overcome these barriers, achieving five- to ten-fold improvements in systemic bioavailability and substantially enhanced antidiabetic efficacy in preclinical models. Emerging mechanistic evidence further positions gut microbiota modulation and epigenetic reprogramming as additional therapeutic axes through which nano-encapsulated phytochemicals may exert durable metabolic benefits. Nonetheless, critical translational challenges persist, encompassing nanotoxicological risks, herb–drug interactions, the absence of harmonised regulatory frameworks for nano-phytomedicine products, phytochemical raw material variability, and formidable technical and economic barriers to scalable nanoparticle manufacturing. This review synthesises the current mechanistic, formulation, and clinical evidence within a unified analytical framework and identifies the strategic priorities of rigorous clinical development, regulatory clarity, and manufacturing standardisation required to translate nano-phytomedicine science into evidence-based T2DM therapeutics. Full article

Polysaccharide derivatives with tunable hydrophobicity offer a versatile platform for tailoring material properties through controlled chemical modification. In this study, pullulan was functionalized with saturated fatty acids (C14-C18) via N,N-carbonyldiimidazole-mediated esterification, yielding degrees of substitution between 0.24 and 0.77. The effect of alkyl chain length and substitution levels on the thermal, structural, and surface properties of the resulting pullulan esters was systematically investigated. Increasing chain length enhanced thermal stability and promoted structural ordering, with stearate-modified pullulan exhibiting melting transitions at 40–42 °C and higher degradation temperatures (≥312 °C). Spin-coated nanoscale coatings (110–150 nm thick) exhibited extremely smooth surfaces (S_a < 1 nm), although differences in solubility influenced solvent evaporation and induced nanostructural variations. Surface wettability increased systematically with alkyl chain length and degree of substitution, resulting in water contact angles between 85° and 105°. All coatings were non-cytotoxic and inhibited bacterial growth at the interface without leaching, suggesting a contact-dependent antibacterial effect. These results establish clear structure–property relationships in pullulan esters, demonstrating that surface wettability, structural ordering, and surface functionality can be systematically adjusted via alkyl chain length and degree of substitution. Full article

Soil salinization constrains agricultural sustainability in coastal low plain regions, yet the mechanisms regulating salt spatial heterogeneity under different water management regimes remain unclear. This study investigated soil soluble ion distribution and influencing factors across 0–200 cm profiles (n = 78) under freshwater irrigation (FWI), brackish water irrigation (BWI), and non-irrigation (NOI) in the North China Plain. We hypothesized that irrigation affects soil salinization through dual pathways: direct ion inputs and indirect modification of soil physicochemical properties. Partial least squares structural equation modeling was used to quantify these effects. Results identified irrigation as an important correlate, exerting a significant direct negative effect on salt accumulation (−0.117) and an indirect effect mediated by soil physicochemical properties (0.218). The three regimes produced markedly distinct soluble ion composition and vertical salt distribution. FWI exhibited a bottom-accumulated distribution of soil salinity. BWI was characterized by significant Na⁺ and Cl⁻ enrichment in the 50–100 cm layer, displaying a mid-profile accumulation pattern despite temporary surface desalination. NOI exhibited the most severe soil sodification, alongside a surface-accumulated profile. These findings reveal a trade-off in coastal water management: brackish water can partially offset freshwater scarcity, but long-term sustainability requires depth-specific salinity monitoring to mitigate subsurface salt accumulation risks. Full article

Soil salinization constrains global wheat production, but how organic–microbial amendments alleviate saline–alkali stress across plant tissues remains poorly characterized. In a single-season field trial, we compared three treatments—a non-saline control (CK), a saline–alkali control (SCK), and an organic fertilizer combined with a microbial inoculant applied to saline–alkali soil (SDM)—to evaluate effects on soil properties, the rhizosphere microbiome structure, leaf antioxidant defense, and grain quality. SDM improved soil nutrient availability: available phosphorus and potassium increased by 96.0% and 51.8%, respectively, relative to SCK, and rhizosphere microbiome shifts favored copiotrophic taxa (Flavobacterium, Devosia, Mortierella) over halotolerant genera (Arthrobacter, Filobasidium). In leaves, SDM induced a controlled antioxidant activation—peroxidase (POD) functioned as a key mediator of oxidative homeostasis, with activities exceeding CK yet remaining below extreme SCK levels—producing the lowest malondialdehyde content (−48.4% vs. SCK). At moderate concentrations, reactive oxygen species participated in developmental signaling rather than causing pathological damage, enabling grain soluble sugars and total starch to be restored to CK levels. These results reveal a coordinated soil–microbiome–plant response in which organic–microbial amendment enhances nutrient cycling, redirects community assembly toward nutrient-cycling functional guilds, and achieves oxidative homeostasis and grain quality restoration. Our findings offer a conceptual basis for the microbiome-informed management of saline–alkali wheat production. Full article

Endocan, a soluble dermatan sulfate proteoglycan, is increasingly recognized as a regulator of key cellular pathways in both physiological and pathological contexts. While TGF-β is a central mediator of fibrotic remodeling, the role of endocan in this process remains elusive. By performing a transcriptomic dataset analysis [GSE116250], we found that endocan expression is upregulated and correlates with fibrotic markers in human failing hearts. We investigated the role of endocan in an in vitro model of cardiac fibroblasts stimulated with TGF-β. Our results identified endocan as a TGF-β-responsive gene in primary human cardiac fibroblasts. Indeed, by inhibiting endocan expression using a specific siRNA, we demonstrated that this proteoglycan is required for the full expression of key fibrosis-related genes (Col1a1, α-SMA, MMP-3, and MMP-9) and modulates the expression of long non-coding RNAs (MALAT1, H19 and HOTAIR), which are essential for the epigenetic control of the fibroblast phenotype. These effects depend on the modulation of both canonical (SMAD3) and non-canonical (AKT and ERK1/2) TGF-β pathways. Taken together, these findings indicate that endocan is required for the coordinated activation of canonical and non-canonical TGF-β signaling during fibroblast transdifferentiation and suggest its potential involvement in the molecular mechanisms underlying cardiac fibrosis. Full article

Developing effective oral formulations for poorly soluble anticancer drugs remains a major pharmaceutical challenge due to the combined limitations of solubility, permeability, and efflux transporter activity. In this work, we investigated the influence of the nonionic surfactants Cremophor EL, Pluronic P-85, and Pluronic F-68 on the solubility and intestinal permeability of the anticancer drug etoposide. All surfactants significantly increased etoposide aqueous solubility. While in vitro permeability across an artificial membrane demonstrated the expected solubility-permeability tradeoff, in vivo SPIP studies in rats revealed a distinctive solubility-permeability interplay for Cremophor EL and Pluronic P-85, which simultaneously enhanced solubility and permeability, likely through P-gp inhibition. In contrast, Pluronic F-68 exhibited the classical solubility-permeability tradeoff, consistent with its reported negligible P-gp inhibitory activity. Mechanistic analysis indicated that surfactant hydrophobicity and molecular weight critically influence P-gp inhibition via ATPase modulation. Surfactants with higher hydrophobicity and moderate molecular weight can integrate into the phospholipid bilayer, enabling direct interaction with P-gp and disruption of its ATPase function. These findings provide strategic insights for the rational design of oral formulations capable of overcoming the solubility-permeability tradeoff, improving the bioavailability of challenging anticancer drugs, and may facilitate the transition from intravenous to oral chemotherapy. Full article