Search Results (20,042)

To develop new hybrid anticancer agents, 3,5-bis(benzylidene)-4-piperidone scaffolds (compounds 1–6) were functionalized with (1R)-borneoyl chloroacetate (8) or (1S)-camphorsulfonyl chloride (10). Covalent attachment of the camphorsulfonyl moiety via N-sulfonylation yielded hybrid molecules (16–21) that exhibited selective cytotoxic and cytostatic activity against cancer cells, with submicromolar IC₅₀ values. In silico ADME analysis indicated that these camphorsulfonyl-conjugated piperidones have improved drug-like properties (enhanced absorption, metabolism, and bioavailability) compared to curcumin. The most potent analogs were halogen-substituted and trimethoxy-substituted analogs, which showed the strongest tumor cell growth inhibition while sparing normal cells. Overall, this terpene-functionalization strategy addresses curcumin’s pharmacokinetic limitations and improves its anticancer profile. These hybrid molecules hold promise as potential anticancer agents. Full article

Peripheral edema is a pathological condition caused by abnormal fluid accumulation in the interstitial space due to elevated vascular permeability and inflammation. This study evaluated the therapeutic efficacy of Terminalia chebula fruit extract (TCE) in inflammation-induced peripheral edema and clarified its molecular mechanisms. Using hydrogen peroxide (H₂O₂)-stimulated human umbilical vein endothelial cells (HUVECs), TCE was tested for effects on cell viability, inflammatory gene expression, intracellular reactive oxygen species, endothelial barrier integrity, and vascular endothelial growth factor (VEGF)-induced migration. Its influence on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling was examined. In vivo, TCE was assessed in acetic acid-induced peritoneal vascular permeability and carrageenan-induced paw edema models, followed by histological analysis and serum tumor necrosis factor-α (TNF-α) measurement. TCE restored cell viability (76.2% to 94.8%), reduced TNF, IL6, and PTGS2 mRNA expression, and decreased reactive oxygen species by 27.2%. It enhanced barrier integrity, increased transendothelial electrical resistance, and inhibited VEGF-induced migration. TCE suppressed NF-κB and MAPK activation. In vivo, TCE reduced Evans blue extravasation by 41.6% and paw edema by 67.5%. Histology showed reduced dermal thickening and inflammatory infiltration, and serum TNF-α levels were lowered. TCE attenuates peripheral edema by preserving endothelial barrier function and suppressing inflammatory signaling, supporting its potential as a therapeutic agent for inflammation-associated vascular dysfunction and edema. Full article

Acmella radicans (Jacquin) R.K.Jansen is an annual herb native to Central America. In China, it is becoming increasingly invasive and often co-occurs with the native congener A. paniculata (Wall. ex DC.) R.K.Jansen in some habitats. In order to understand the invasion mechanism of A. radicans, we investigated the growth parameters of both the invasive A. radicans and the native congener, A. paniculata, under different light conditions (5%, 25%, 50%, 75%, and 100% of light availability) using potted plants in a glasshouse. Light level, plant species, and their interaction were significant, with plant species generally having a greater effect than light level. Acmella radicans and A. paniculata showed great phenotypic plasticity to various light intensities and had a similar trend with increased shade. The plasticity indices of all parameters of A. radicans, except for branch length and inflorescence number, were greater than those of A. paniculata under the same light intensity. The physiological parameters for A. radicans under both favorable (high light intensity) and unfavorable (low light intensity) conditions showed less inhibition than those of A. paniculata. All these responses indicated that A. radicans had greater phenotypic plasticity and higher adaptability to low light, which may contribute to its invasion success. Full article

The antibacterial properties of Ag(I) coordination compounds are well documented; however, their effectiveness is highly dependent on the choice of appropriate ligands, and it is frequently hindered by their low water solubility and limited bioavailability. Herein, six new Ag(I) complexes incorporating the quinazolinone thioamide mqztH (=2-mercapto-4(3H)-quinazolinone) and phosphine co-ligands were synthesized and investigated for their antibacterial activity. In vitro activity assays against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacterial strains revealed that all complexes selectively inhibited S. aureus bacterial growth. Structure–activity relationship analysis showed that monodentate PPh₃ co-ligands play a key role in enhancing the antibacterial efficacy of their complexes. Notably, complex [AgCl(mqztH)(PPh₃)₂] (1) exhibited broad-spectrum activity, with IC₅₀ values of 4.2 ± 1.4 μg mL^–1 (4.9 μΜ) for S. aureus and 63 ± 1.9 μg mL^–1 (75 μΜ) for E. coli bacteria. To improve solubility and antibacterial activity, complex 1 was encapsulated in barium alginate (BaAlg) matrices to form hydrogel-based drug delivery formulations [¹]@BaAlg. The synthesized formulations retained the bactericidal effect of the complex, achieving comparable activity at concentrations lower by an order of magnitude compared to complex 1 in free form. Combined with the demonstrated high biocompatibility of complex 1 toward L929 normal eukaryotic cells, as well as the biocompatible nature of the alginate matrix, these findings underscore the strong potential of the complex 1-loaded hydrogel formulations for further investigation and development as effective antibacterial drug platforms. Mechanistic studies confirmed the redox-active nature of complex 1 and its potential to inhibit the function of glutathione reductase (GR) and thioredoxin reductase (TrxR) at low concentrations, suggesting the interference with bacterial redox homeostasis as a relevant mechanism of bioactivity. Full article

Light plays an essential role in regulating the growth, development, and metabolic activities of the edible mushroom Pleurotus ostreatus. In this research, the influence of white, blue, green, yellow, and red light, and darkness, on the global protein expression of P. ostreatus LGAM 1123 grown in submerged culture was explored. The growth of the fungus was not inhibited by light in any of the conditions tested compared with the dark. However, the mycelial protein content was reduced by 10% under blue and white light. Proteomic analysis revealed distinct proteomes for each light wavelength, with red and blue light presenting the most distinctive proteome profiles. (Data are available via ProteomeXchange with identifier PXD065402.) Blue light activates pathways such as the citrate cycle (TCA cycle), glycolysis/gluconeogenesis, and amino acid biosynthesis, while red light stimulates mRNA-related pathways. GC-MS analysis of the biomass revealed differences in the amino acids, sugars, and lipids produced. The distinct regulation of proteins and bioactive compounds under different light wavelengths suggests that specific wavelengths can direct the metabolism of P. ostreatus into biochemical pathways. These strategies could be beneficial for the food industry because particular nutrients can be increased during the fermentation of edible fungi without the need for genetic engineering of the strain. Full article

Background: Low temperature stress is a major environmental challenge affecting the growth, metabolism, and survival of many aquaculture species, including Nile tilapia (Oreochromis niloticus). Understanding the molecular mechanisms underlying cold tolerance is therefore essential for improving fish resilience and aquaculture sustainability. Methods: In the present study, an acute cold stress model of Nile tilapia (Oreochromis niloticus) was established and it was found that uncoupling protein 1 (UCP1) was involved in the acute cold stress process of tilapia. Results: The upregulation of UCP1 in the liver under cold stimulation was regulated by stress hormones such as cortisol and adrenaline. UCP1 has a short half-life and is degraded by proteasomes. In tilapia primary hepatocytes, the addition of adrenergic receptor agonists resulted in mitochondrial membrane potential decreasing, while UCP1 siRNA transfection inhibited mitochondrial membrane potential. Biochemical characteristics indicate that UCP1 is a channel protein that mediates proton leakage. In addition, feeding and intraperitoneal injection of mitochondrial uncoupling agent BAM15 can alleviate the low-temperature stress of tilapia. Conclusions: UCP1 helps maintain the metabolic homeostasis of tilapia under acute cold stimulation and provides new insights into the mechanisms of cold resistance as well as potential treatment strategies in fish. Full article

Architectural exterior wall coatings require a balance of elasticity, stain resistance, and durability. Although nano-SiO₂ enhances fracture resistance in elastic coatings, its limited hydrophobicity allows pollutant adhesion. Nano-TiO₂ can photocatalytically degrade organics but is often encapsulated by the polymer matrix, reducing its effectiveness. This study introduces a SiO₂-TiO₂ composite topcoat applied via aqueous dispersion to overcome these limitations. Experimental results demonstrate that the composite coating significantly outperforms single-component modifications, improving stain resistance by 21.3% after 12 months of outdoor exposure. The surface remains brighter with markedly reduced pollutant accumulation. Mechanistically, SiO₂ serves as an inert mesoporous carrier that improves the dispersion and photostability of TiO₂, minimizing agglomeration and photocorrosion. Its inherent hardness and hydrophobicity reduce physical adsorption sites. Together, SiO₂ and TiO₂ create a nanoscale rough surface that enhances hydrophobicity through a lotus-like effect. Under UV irradiation, TiO₂ generates radicals that decompose organic pollutants and inhibit microbial growth, enabling efficient self-cleaning with rainwater. This synergistic mechanism addresses the limitations of individual nanoparticles, successfully integrating elasticity with long-term anti-fouling and durability. This composite demonstrates a significant advancement in stain resistance and overall durability, offering potential applications in energy-efficient and environmentally sustainable building technologies. Full article

Chrysanthemum (Chrysanthemum morifolium Ramat.), a typical short-day plant (SDP), relies on photoperiod and light quality signals to regulate flowering and growth. Red light interruptions inhibit its flowering, whereas supplemental blue light can counteract this inhibitory effect. To investigate how “high-blue/low-red” mixed light (RBL) regulates chrysanthemum flowering and growth, we treated ‘Gaya Glory’ plants with 4 h of supplemental or night-interruptional RBL (S-RBL4 or NI-RBL4, 0 or 30 ± 3 μmol m⁻² s⁻¹ PPFD) under 10 h short-day and 13 h long-day conditions (SD10 and LD13; white light, WL; 300 ± 5 μmol m⁻² s⁻¹ PPFD), recorded as SD10, SD10 + S-RBL4, SD10 + NI-RBL4, LD13, LD13 + S-RBL4, and LD13 + NI-RBL4, respectively. Under SD10 conditions, S-RBL4 promoted flowering and enhanced nutritional quality, whereas NI-RBL4 suppressed flowering. Under LD13 conditions, both treatments alleviated flowering inhibition, with S-RBL4 exhibiting a more pronounced inductive effect. Chrysanthemums displayed superior vegetative growth and physiological metabolism under LD13 compared to SD10, as evidenced by higher photosynthetic efficiency, greater carbohydrate accumulation, and more robust stem development. Furthermore, S-RBL4 exerted a stronger regulatory influence than NI-RBL4 on photosynthetic traits, the activities of sugar metabolism-related enzymes, and gene expression. The photoperiodic flowering of chrysanthemum was coordinately regulated by the photoreceptor-mediated and sugar-induced pathways: CmCRY1 modulated the expression of florigenic genes (CmFTLs) and anti-florigenic gene (CmAFT) to transmit light signals, while S-RBL4 activated sucrose-responsive flowering genes CmFTL1/2 through enhanced photosynthesis and carbohydrate accumulation, thereby jointly regulating floral initiation. The anti-florigenic gene CmTFL1 exhibited dual functionality—its high expression inhibited flowering and promoted lateral branch and leaf growth, but only under sufficient sugar availability, indicating that carbohydrate status modulates its functional activity. Full article

Black spot is currently one of the most widespread diseases affecting Yanbian Pingguoli pears (Pyrus pyrifolia cv. ‘Pingguoli’), resulting in significant economic losses for fruit farmers. It is mainly caused by infestation by the fungal group of Alternaria species. To date, no research has reported the presence of Alternaria species and the pathogen of black spot disease on Yanbian Pingguoli pears in China. This study isolated, identified, and performed molecular profiling of 124 Alternaria strains collected from 15 major growing areas of Yanbian Pingguoli pear (more than 5000 trees). Moreover, the study evaluated the ability of Artemisia capillaris essential oil (AcEO) to suppress the mycelial expansion of Alternaria pathogens and conducted comprehensive chemical profiling. Overall, 124 pathogenic fungi were identified as Alternaria tenuissima (67 isolates, 54.0%) and A. alternate (57 isolates, 46.0%). AcEO showed a strong inhibitory effect on the two Alternaria species, with a minimal inhibitory concentration (MIC) value equivalent to 5.0 μL/mL. Eucalyptol, 2,2-Dimethyl-3-methylenebicyclo [2.2.1] heptane, (-)-alcanfor, and β-copaene were identified as the predominant bioactive components of AcEO. AcEO demonstrated concentration-dependent inhibition of the mycelial growth of A. tenuissima and A. alternata. These findings position AcEO as a promising candidate for developing sustainable fungicides to combat Alternaria-induced crop losses. Full article

Background/Objectives: This study systematically investigated the expression characteristics of the ALDOA gene in skeletal muscle cells and its effects on cell proliferation, apoptosis, and differentiation. Methods: We constructed an ALDOA overexpression vector and transfected it into C2C12 cells and porcine skeletal muscle satellite cells. Results: We found that ALDOA exhibited the highest expression in the longissimus dorsi muscle and was primarily localized in the cell nucleus. Overexpression of ALDOA significantly inhibited cell proliferation, induced G0/G1 phase arrest, and downregulated the expression of proliferation-related genes such as CDK2 and Cyclin D1. Concurrently, ALDOA overexpression markedly promoted apoptosis. Regarding differentiation, although ALDOA expression was upregulated during differentiation, its overexpression significantly suppressed the expression of myogenic differentiation-related genes (such as MYOD, MYOG, MEF2C), suggesting a negative regulatory role in differentiation control. Conclusions: This study reveals the multifaceted regulatory functions of ALDOA in skeletal muscle cells, providing experimental evidence for deepening the understanding of its mechanisms in muscle development and regeneration. This study provides the first functional evidence that ALDOA acts as a multifunctional regulator in skeletal muscle cells, negatively governing cell growth and fate decisions by inhibiting proliferation, promoting apoptosis, and impeding myogenic differentiation, thereby extending its role beyond glycolysis to direct governance of cellular processes. This study reveals for the first time that ALDOA possesses dual functions in muscle cells, regulating both metabolism and transcription. Full article

Objectives: The aim of this study was to review the importance of peritoneal fluid steroid hormone concentrations to understand the mechanism of hormonal medical treatment of endometriosis-associated pain. Design: The study included a PubMed search and a pilot trial in 8 adolescents. Results: Oral contraceptives (OCs) were designed to inhibit ovulation in all women, and doses are much higher than the mean ovulation-inhibiting dose. Therefore, in most women, half a dose and in some women, even less is sufficient to inhibit ovulation. The inhibition of ovarian function and ovulation decreases estrogen and progesterone concentrations in plasma and peritoneal fluid. Surprisingly, the effect on peritoneal fluid steroid hormone concentrations has not been considered to explain the impact on endometriosis-associated pain. The lowering of the high estrogen concentrations in peritoneal fluid is sufficient to explain the pain decrease in superficial and ovarian endometriosis. A direct progesterone effect is unlikely, given the high progesterone concentrations in the peritoneal fluid of ovulatory women. In 8 adolescents, half an OC dose resulted in an apparently similar pain relief as a full dose (personal observation). Conclusions: The decrease in ovarian and superficial pelvic endometriosis-associated pain with OCs can be explained by lowering the intra-ovarian and the high estrogen concentrations in peritoneal fluid after ovulation. A direct progesterone effect is unlikely. Since OCs are severely overdosed in most women, half a dose is sufficient in most with fewer side effects, permitting individualization of therapy in women not requiring contraception. Understanding peritoneal fluid also explains that hormone replacement therapy is not contraindicated in most women with a history of endometriosis. Since the mechanisms of medical therapy of endometriosis-associated pain and the prevention of progression might be different, the growth of lesions must be monitored during treatment. Full article

Background: Diabetes-related foot diseases represent a global health problem because of the associated complications, the risk of amputation, and the economic burden on health systems. Negative pressure wound therapy (NPWT) is a technique that uses sub-atmospheric pressure to help promote wound healing by reducing the inflammatory exudate while keeping the wound moist, inhibiting bacterial growth, and promoting the formation of granulation tissue. Objective: This study aimed to assess the effectiveness of NPWT in preventing major amputation in diabetic patients with complicated foot or lower limb infections and to contextualize the results through a review of the existing literature. Materials and methods: We conducted a retrospective study at the First Surgical Department of “Dr. I. Cantacuzino” Clinical Hospital in Bucharest, Romania, over a 15-year period, including 30 consecutive adult patients with diabetes and soft tissue foot or lower limb infections treated with NPWT. Patients with non-diabetic ulcers, incomplete medical data, or aged under 18 were excluded. All patients underwent initial surgical debridement, minor amputation, or drainage procedures, followed by the application of NPWT using a standard protocol. Dressings were changed every 2–4 days for a total of 7–10 days. Antibiotic therapy was adapted according to the culture results. The primary outcome was limb preservation, defined as avoidance of major amputation. Secondary outcomes included in-hospital mortality and wound status at discharge. Results: NPWT was associated with a favorable outcome in 24 patients (80%), defined by wound granulation or healing without the need for major amputation. Five patients (16.6%) underwent major amputation because of failure of the primary lesion treatment, and one patient died. No statistically significant association was observed between the outcomes and standard classification scores (WIFI, IWGDF, and TPI). A comprehensive literature review helped to integrate these findings into the existing pool of knowledge. Conclusions: NPWT may support limb preservation in selected diabetic foot cases. While the retrospective design and the small sample size of the study limit generalizability, these results reinforce the need for further controlled studies to evaluate NPWT in real-life clinical settings. The correct use of NPWT combined with etiological treatment may offer a maximum chance to avoid major amputation in patients with diabetes-related foot diseases. Full article

Leaf senescence is a precisely regulated developmental process that is critical for grapevine growth and yield, which is easily influenced by environmental factors. High temperature is a major factor that accelerates senescence rapidly, adversely affects photosynthetic performance, severely hindering fruit nutrient metabolism and growth. This study investigated chlorophyll fluorescence and physiological traits in grape (Vitis vinifera L.) leaves at different senescence stages under natural high-temperature conditions in Turpan. Measurements included chlorophyll content, MDA levels, antioxidant enzyme activities, and chlorophyll fluorescence parameters. The results showed that (1) young leaves exhibited higher and more sustained chlorophyll content but were prone to wilting, whereas older leaves showed accelerated chlorosis and functional decline; (2) high temperature severely impaired PSII function, inhibiting electron transport and photochemical efficiency, reflected in increased ABS/RC, TR_o/RCC, and DI_o/RC, and decreased F_v/F_m, F_v/F_o, and PI_abs; (3) POD, SOD, CAT and MDA levels initially increased then decreased, correlating with photosynthetic changes and leaf age; and (4) young leaves maintained stronger photosynthetic capability and physiological resilience than older ones. Although partial recovery occurred after temperature reduction, photosynthetic and antioxidant activities did not fully revert. This suggests persistent heat-induced functional decline and accelerated senescence, providing insights for understanding heat-induced leaf senescence and developing strategies for cultivating grapevines. Full article

Myofibroblasts drive wound healing and fibrotic disease through generation of contractile force to promote wound closure and production of matrix proteins to generate scar tissue. Platelets secrete many pro-wound healing molecules, including cytokines and growth factors. We previously reported that inorganic polyphosphate, secreted by activated platelets, is chemotactic for fibroblasts and induces a myofibroblast phenotype. Using NIH-3T3 cells and primary human fibroblasts, we examined the impact of inhibitors of cell-surface receptors and intracellular signaling molecules on polyphosphate-induced myofibroblast differentiation. We now report that polyphosphate-induced differentiation of fibroblasts to myofibroblasts occurs through a signaling pathway mediated by the receptor for advanced glycation end products (RAGE) and nuclear factor kappa B (NFκB) transcription factor. Inhibition of these signaling components ablated the effects of polyphosphate on fibroblasts. Platelet releasates also induced NFκB signaling and myofibroblast differentiation. Blocking the polyphosphate content of platelet releasates with a biocompatible polyP inhibitor rendered the releasates unable to induce myofibroblast differentiation. These results identify a cell-surface receptor and intracellular transcription factor utilized by platelet polyphosphate to promote wound healing through myofibroblast differentiation and may provide targets for promoting wound healing or altering the disease progression of fibrosis. Full article

With the rapid increase in the synthesis and application of graphene oxide (GO), questions have emerged about its inadvertent entry into aquatic habitats and the ecological consequences associated with such exposure While several studies have addressed the acute effects of GO, knowledge on its chronic impacts across multiple trophic levels remains limited. In this study, we assessed the chronic toxicity of a well-characterized GO product using model organisms representing three trophic levels: the bioluminescent marine bacterium Aliivibrio fischeri, unicellular green algae (Chlamydomonas reinhardtii, Chlorella vulgaris, Desmodesmus subspicatus), the cyanobacterium Synechococcus elongatus, and the freshwater cladoceran Daphnia magna. Endpoints included bioluminescence inhibition in bacteria, growth inhibition in photosynthetic primary producers, and reproduction and refined physiological parameters (heart rate, feeding activity) in D. magna. Our results demonstrated clear concentration-dependent chronic effects of GO, with A. fischeri, the applied photosynthetic primary producers and D. magna exhibiting significant inhibition of bioluminescence, growth, delayed onset of reproduction, and reduced fitness parameters, respectively. Based on the collected data, a comprehensive ecotoxicological risk assessment was carried out, revealing that pristine GO may pose negligible hazard to aquatic ecosystems under environmentally relevant exposure scenarios. The outcomes clearly demonstrate the relevance of incorporating chronic and multi-trophic effects when evaluating the ecological risks of emerging nanomaterials such as GO. Full article