Search Results (13,940)

Laying hens in the late laying period often experience reduced productivity and declining egg and meat quality, which limits breeding efficiency and resource utilization. This study aimed to evaluate the effects of multi-component Botanical Crude Extracts (BCEs) on egg and meat quality, metabolic health, and gut microbiota in aged laying hens. A total of 4320 hens were supplemented with 0.3% BCEs for 100 days, with evaluations at 60 and 100 days. BCE supplementation significantly enhanced egg flavor by promoting aromatic and fat-soluble volatiles and reducing odorous compounds (p < 0.05). BCEs improved yolk nutrition by enriching n-3 polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), and optimizing the n-6/n-3 ratio (p < 0.05). A moderate reduction in amino acids was observed, which may reduce bitterness and ammonia burden (0.05 ≤ p < 0.10, trend). In muscle, BCEs improved protein–fat distribution, increased intramuscular fat, and enhanced flavor-related metabolites, significantly improving meat quality of culled hens (p < 0.05). BCEs also reshaped gut microbiota, reducing harmful taxa and promoting short-chain fatty acid and aromatic metabolite biosynthesis (p < 0.05). Serum metabolomics revealed modulation of AMPK, calcium, and cholesterol pathways, improving antioxidant capacity and lipid regulation (p < 0.05). Correlation analyses linked beneficial bacteria and metabolites with yolk DHA levels and flavor (p < 0.05). Overall, BCEs enhanced egg and meat quality and physiological health, providing guidance for functional feed strategies in aged laying hens. Full article

Background: The COVID-19 pandemic significantly impacted adolescent development, increasing behavioral problems and emotional distress. This study aimed to examine the impact of sensation seeking, empathy, and COVID-19-related stressors on deviant behavior in adolescents. Methods: A cross-sectional study was conducted with 638 Italian adolescents and young adults (M = 18.8 years, SD = 3.51) recruited from schools, universities, and the general population in Tuscany and Emilia-Romagna. Participants completed validated measures assessing sensation seeking, empathy, COVID-19-related stress, and deviant behaviors. Multiple regression analyses examined predictors of deviant behavior, while mediation analyses tested whether empathy mediated the relationship between sensation seeking and deviant behavior. Results: Correlation analyses show a positive association between sensation seeking and deviant behavior and a weaker positive association with COVID-19 isolation. Conversely, affective empathy demonstrated negative correlations with both deviant behavior and sensation seeking. COVID-19 stress demonstrated differentiated effects: social isolation increased deviance, whereas fear of contagion was protective. Mediation analysis revealed that affective empathy partially mediated the relationship between sensation seeking and deviance. Conclusions: This study demonstrates that sensation seeking is a primary risk factor for deviant behavior in adolescents and young adults, while affective empathy acts as a protective mechanism that partially mediates this relationship. Furthermore, COVID-19-related stressors have shown complex effects, with social isolation amplifying the risk of deviance, while fear of contagion promotes more inhibited behavior. These findings underscore the importance of considering both stable personality traits and situational stressors when seeking to understand the pathways leading to adolescent behavioral problems during periods of social crisis. Full article

Phthalic acid esters (PAEs) are important plasticizers that have led to the heavy pollution of farmland, which has aroused significant and widespread concern for soil health and food safety. Microbial degradation has been recognized as an efficient pathway for removing PAEs from the environment. In this study, the PAE-degrading strain FR1 was isolated from sewage and determined to belong to Glutamicibacter. This strain degraded PAEs efficiently under a wide range of conditions—10–50 °C, pH of 6.0–11.0, and 0–8% salinity—demonstrating its great potential in PAE bioremediation. Genome sequencing provided complete genomic information, showing that the strain comprises one chromosome (3,404,214 bp) and three plasmids (112,089 bp, 80,486 bp, and 40,002 bp). The chromosome harbors 3238 protein genes, of which the PAE hydrolase genes dphGB1 and mphGB2 have been cloned. The hydrolase DphGB1 from hydrolase family I contained the catalytic triad Ser75-Asp194-His221. After heterogeneous expression and purification, the recombinant protein DphGB1, of about 30 kDa, was obtained. This hydrolase showed strong hydrolytic ability toward DEHP. The protein MphGB2 could also hydrolyze MBP. The molecular docking revealed interaction between DphGB1 and DBP. The main hydrolases of strain FR1-degrading PAEs were functionally identified. These results will promote the elucidation of the catalytic mechanisms of PAE hydrolases and the application of strain FR1 in farmland soil remediation. Full article

Background: Gallic acid (GA) is a dietary polyphenol widely found in walnuts, tea leaves, and grapes, and it is recognized for its potent antioxidant and anti-inflammatory properties. Chronic sleep deprivation (CSD) is known to disrupt redox balance, promote neuroinflammation, and impair cognition, while effective nutritional strategies to mitigate these effects remain scarce. This study was designed to evaluate the protective potential of GA against CSD-induced cognitive deficits in mice and to elucidate the underlying mechanisms. Methods: Seventy-two male ICR mice were randomly allocated to six groups, including control, CSD model, Ginkgo biloba extract, and GA at three doses (50, 100, and 200 mg/kg). After 28 days of treatment, cognitive performance was assessed using the open field test (OFT), novel object recognition (NOR), step-through passive avoidance (ST), and Morris water maze (MWM). Redox status and inflammatory mediators were determined by ELISA, while the hippocampal expression of proteins related to antioxidant defense and NF-κB signaling was analyzed by Western blotting. Results: GA supplementation improved exploratory activity, recognition memory, and spatial learning in the CSD mice. Biochemical evaluation revealed that total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity were restored, while malondialdehyde (MDA) levels, an indicator of lipid peroxidation, were reduced. These changes were accompanied by decreased circulating concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). At the molecular level, GA enhanced the expression of Nrf2, HO-1, and NQO1, while inhibiting p-p65, iNOS, and COX2 in the hippocampus. Conclusions: These findings demonstrate that GA alleviates CSD-induced cognitive deficits through the activation of the Nrf2/HO-1 antioxidant pathway and inhibition of NF-κB–mediated inflammatory responses. Thus, GA may represent a promising nutraceutical candidate for maintaining cognitive health under chronic sleep loss. Full article

Cancer is a multifaceted disease characterized by uncontrolled cell division resulting from substantial disruptions of normal biological processes. Central to its development is cellular transformation, which involves a dynamic sequence of events including chromosomal translocations, genetic mutations, abnormal DNA methylation, post-translational protein modifications, and other genetic and epigenetic alterations. These changes compromise physiological regulatory mechanisms and contribute to accelerated tumor growth. A critical factor in this process is the dysregulation of transcription factors (TFs) which regulate gene expression and DNA transcription. Dysregulation of TFs initiates a cascade of biochemical events, such as abnormal DNA replication, that further enhance cell proliferation and increase genomic instability. This microenvironment not only sustains tumor growth but also promotes the accumulation of somatic mutations, thereby fueling tumor evolution and heterogeneity. In this study, we employed an in silico approach to identify TFs regulating 622 key genes whose mutations are implicated in carcinogenesis. Transcriptional regulatory networks were analyzed through bioinformatics methods to elucidate molecular pathways involved in cancer development. A thorough understanding of these processes may help to clarify the function of dysregulated TFs and facilitate the development of novel therapeutic approaches designed to make cancer treatments personalized and efficacious. Full article

Although extracellular vesicles (EVs) from mesenchymal stem cells have shown potential in skin wound repair, the diversity of EV sources and the optimization of delivery systems still need further exploration. This study is the first to demonstrate that extracellular vesicles from chemically induced mammary epithelial cells (CiMECs-EVs) possess distinct skin wound repair activity. To enhance the therapeutic efficacy of CiMECs-EVs and optimize their delivery efficiency, we innovatively combined them with a chitosan hydrogel to construct a composite repair system (CiMECs-EVs-chitosan hydrogel, CMECG). This system was then applied to a rat skin wound model. The results showed that CMECG significantly promoted the proliferation and migration of fibroblasts and mammary epithelial cells (MECs). In animal experiments, the relative wound closure efficiency of the control group was approximately 70% on day 14, while that of the CMECG group (loaded with 200 μg CiMECs-Exo) was enhanced to 90%, markedly accelerating the wound healing process. Histological analysis indicated that this system could effectively restore the structural continuity of various skin layers and significantly promote the synthesis and remodeling of collagen at the wound site. Mechanistically, the wound healing effect of CiMECs-EVs is closely associated with the endogenous miRNAs they encapsulate. These miRNAs can coordinately regulate cell proliferation, migration, and angiogenesis, modulate the inflammatory microenvironment, and inhibit excessive scar formation—thus regulating the entire repair process. This process involves multiple wound healing-related signaling pathways, including MAPK, PI3K-Akt, FoxO, TGF-β, and JAK-STAT. In summary, this study successfully constructed a novel EV-chitosan hydrogel repair system. This system is expected to provide an effective and innovative EV-based therapeutic strategy for the clinical treatment of skin wound repair. Full article

Polycystic ovary syndrome (PCOS) is a systemic metabolic and endocrine disorder that significantly disrupts reproductive physiology and endometrial function. In this narrative review, we examine the molecular impact of metabolic and hormonal imbalances on the endometrium of women with PCOS. We investigate the specific mechanisms that delineate how hyperinsulinemia and insulin resistance, chronic low-grade inflammation, and estrogen/progesterone/androgen imbalance contribute to altered epigenetic, transcriptomic, metabolomic, and signaling profiles in a wide array of different cell types within endometrial tissues. The synergistic interplay between upregulated inflammatory cytokines (e.g., IL-1,2,6,8,17,18, and TNF-α), along with key changes in critical molecular pathways associated with hyperinsulinemia and insulin resistance (e.g., PI3K/AKT/MAPK, and Wnt/β-catenin), in addition to aberrant sex steroid hormone signaling (e.g., CYP19A1, COX-2, PGE₂, HOXA10, 11βHSD2), promotes deleterious changes within the endometrial microenvironment. These anomalies underpin a spectrum of clinical manifestations observed in women with PCOS at each stage of the life course, including abnormal uterine bleeding in reproductive-age women, impaired decidualization in pregnancy, and altered postmenopausal endometrial physiology. Clinically, these alterations are associated with abnormal uterine bleeding, subfertility, implantation failure, miscarriage, pregnancy complications, and postmenopausal endometrial hyperplasia and cancer. Overall, our review provides novel insights into the molecular mechanisms linking systemic metabolic and endocrine dysfunction with endometrial pathology in PCOS and has broader implications that apply to all women. Full article

Background/Objective: Larazotide acetate (LA) is a synthetic octapeptide under development as a therapeutic candidate for celiac disease, acting to reduce intestinal permeability and regulate tight junctions (TJs). Although several studies have shown barrier-protective effects, the cellular mechanisms underlying LA’s actions in the intestinal epithelium remain unclear. This study aimed to elucidate the mechanistic roles of LA in maintaining intestinal epithelial integrity during cellular injury. Methods: C2BBe1 and leaky IPEC-J2 cell monolayers were pretreated with 10 mM LA and subjected to anoxia/reoxygenation (A/R) injury. Transepithelial electrical resistance (TEER), TJ protein localization, and phosphorylation of myosin light chain-2 (MLC-2) were analyzed. In addition, RNA sequencing was conducted to identify differentially expressed genes and signaling pathways affected by LA treatment. Results: LA pretreatment significantly increased TEER and preserved TJ protein organization during A/R injury. Transcriptomic analysis revealed enrichment of genes related to barrier regulation, small GTPase signaling, protein phosphorylation, proliferation, and migration. LA pretreatment markedly reduced MLC-2 phosphorylation, likely through modulation of the ROCK pathway, consistent with RNA-seq findings. Moreover, LA enhanced cellular proliferation, validating transcriptomic predictions. Conclusions: LA exerts a protective effect on intestinal epithelial integrity by stabilizing tight junctions, reducing MLC-2 phosphorylation, and promoting epithelial proliferation. These findings highlight a novel mechanism for LA and support its therapeutic potential in treating gastrointestinal disorders associated with “leaky gut” and mucosal injury. Full article

In our previous study, we demonstrated that a standardized ethanol extract of Perilla frutescens var. acuta (PE) alleviates memory deficits in an Alzheimer’s disease mouse model by inhibiting amyloid β (Aβ) aggregation and promoting its disaggregation. However, the extent to which PE exerts additional cognitive benefits independent of Aβ pathology remained unclear. Here, we aimed to evaluate the effects of PE on synaptic plasticity and learning and memory functions. Male ICR mice were used, and cognitive impairment was induced by scopolamine administration. PE was orally administered at doses determined from previous studies, and cognitive performance was assessed using the passive avoidance, Y-maze, and Morris water maze tests. In parallel, hippocampal slices were employed to examine the effects of PE on synaptic plasticity. PE (100 and 300 μg/mL) significantly enhanced long-term potentiation (LTP) in a concentration-dependent manner without altering basal synaptic transmission. This facilitation of LTP was blocked by scopolamine (1 μM), a muscarinic acetylcholine receptor (mAChR) antagonist, and IEM-1460 (50 μM), a calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (CP-AMPAR) inhibitor, indicating the involvement of mAChR and CP-AMPAR pathways. In vivo, PE (100, 250, and 500 mg/kg) treatment improved memory performance across all behavioral tasks and upregulated hippocampal synaptic proteins including GluN2B, PSD-95, and CaMKII. Collectively, these results demonstrate that PE ameliorates scopolamine (1 mg/kg)-induced cognitive impairment by enhancing synaptic plasticity, likely through modulation of mAChR, CP-AMPAR, and NMDA receptor signaling. These findings highlight the therapeutic potential of PE for memory deficits associated with cholinergic dysfunction. 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

Few studies have explored the holistic public health risk assessment associated with toxic elements (TEs) and their bioaccessibility in integrated urban environmental media including soils, vegetables, atmospheric particles, dust, etc. Urban industrial complex areas like Qingshan-Chemical District (QCD) in the Chinese Wuhan city, located within the Yangtze River Economic Belt, face increasing environmental exposure risks due to industrial activities. This study innovatively assessed the hierarchical risks of toxic metals in 4 environmental media (air PM, dust, soil, vegetables) from the QCD based on field sampling and chemical analysis, and developed an improved fuzzy health risk assessment model based on toxic metals’ in vitro bioaccessibilities of different exposure pathways and triangular fuzzy numbers for handling parameter uncertainties. The study found that the highest health risks were associated with ingestion, particularly from consuming homegrown vegetables. Carcinogenic risks for arsenic (As), lead (Pb), and cadmium (Cd) via ingestion exceeded the admissible threshold of 1.00 × 10⁻⁶, with As showing the highest risk ([1.92 × 10⁻³, 2.37 × 10⁻³]), followed by Cd ([2.98 × 10⁻⁵, 3.67 × 10⁻⁵]) and Pb ([7.92 × 10⁻⁷, 1.48 × 10⁻⁶]). Inhalation risks from soil, dust, and air particulates were below the threshold, indicating lower respiratory concerns. Dermal exposure, especially from soil and dust, posed elevated carcinogenic risks for As ([7.47 × 10⁻⁶, 8.06 × 10⁻⁶]). With the screened priority risk control toxic metals and pathways, the targeted measures including relocating vegetable planting areas, promoting cultivation of low-enrichment crops, building vegetation buffer zones around the industrial park, etc., were proposed. Full article

NAC transcription factors are key regulators involved in diverse cellular processes, stress responses, and developmental pathways in plants. However, their roles in female cone development of Torreya grandis, a representative gymnosperm species, remain largely unexplored. In this study, we performed a comprehensive identification and analysis of NAC transcription factors in T. grandis to investigate their potential functions in female cone development. A total of 82 TgNAC members containing conserved NAM domains were identified, distributed unevenly across 11 chromosomes. Phylogenetic analysis with Arabidopsis NACs classified them into 15 groups, with TgNACs represented in 10 groups and showing a notable enrichment in the TERN clade on chromosome 2. Promoter cis-element analysis revealed correlations between regulatory elements and expression patterns. Tissue-specific expression profiling indicated clear functional specialization, with some TgNACs showing no detectable expression in the examined tissues. During female cone development, several TgNACs were highly expressed in the early stages, whereas TgNAC72, TgNAC76 and TgNAC82 were upregulated during the latter stages. Among these, TgNAC72 exhibited the highest overall expression level. Subcellular localization confirmed TgNAC72 is localized in the nucleus. Dual-luciferase assays further demonstrated that TgNAC72 activates the TgBGLU13 promoter, suggesting its role in starch and sucrose metabolism. Collectively, these findings provide novel insights into the regulatory involvement of TgNACs in reproductive organ development. Full article

RBL1 (p107) is a member of the retinoblastoma (RB) family of pocket proteins involved in cell cycle regulation and E2F transcriptional repression. While its promoter contains conserved E2F motifs, the integrated regulation of RBL1 by upstream tumor suppressor pathways remains incompletely understood. Here, we investigate the p53-dependent transcriptional regulation of RBL1 and dissect the contribution of its tandem E2F binding sites to this mechanism. Luciferase assays in synchronized cells demonstrated that these two conserved E2F sites are required for cell cycle-dependent activation of the RBL1 promoter. Overexpression of p53 showed that p53 represses RBL1 promoter activity in an E2F site-dependent manner. Using HCT116 p21 knockout cells, we revealed that this p53-dependent repression is mediated by p21. Chromatin immunoprecipitation confirmed dynamic in vivo binding of E2F1–3 and E2F4, while DNA pull-down assays revealed specific in vitro recruitment of RB, p107, and E2F1-4 to the two E2F sites, along with weak binding of MuvB components. Additional experiments in RB^–/– and LIN37^–/– knockouts showed that RB/E2F repressing complex plays the main role in repressing the RBL1 promoter, while E2F4, p107, and p130 can support this effect to a lesser extent. Overall, our findings demonstrate that p53 controls RBL1 expression indirectly through the p21–RB–E2F pathway by utilizing two E2F binding sites within the RBL1 promoter. Full article

L-fucose is a monosaccharide derived from brown algae and has potential applications as a functional food ingredient. Previous studies have reported that L-fucose reduces lipid accumulation in murine adipose tissue. Adipose tissue not only regulates energy metabolism but also functions as an endocrine organ involved in inflammation through the production and secretion of various adipokines. L-fucose is expected to exert anti-inflammatory effects and modulate adipokine secretion in adipocytes. In the present study, we investigated the anti-inflammatory effects of L-fucose in adipocytes. L-fucose significantly suppressed the expression of pro-inflammatory mediators and reduced the production of reactive oxygen species induced by inflammatory stimulation with a combination of lipopolysaccharide (LPS), tumor necrosis factor-⍺ (TNF-⍺), and interferon-γ (IFN-γ). These effects are likely mediated through the inhibition of key signaling pathways, including mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) pathways. Additionally, we found that L-fucose promoted the multimerization and secretion of high molecular weight (HMW) adiponectin, even under inflammatory conditions. Our results suggest that although L-fucose downregulates adiponectin expression, it contributes to the formation and/or stabilization of HMW adiponectin, which is functionally more relevant in anti-inflammatory and metabolic regulation. L-fucose thus holds promise as a functional food ingredient for mitigating inflammation in adipocytes. Full article

Previous research has demonstrated that the transient bilateral common carotid artery occlusion and reperfusion (BCCAO/R) effectively models early brain inflammation resulting from sudden hypoperfusion and subsequent reperfusion. According to studies showing that diet and nutrition strongly influence brain neuroplasticity, in this study we evaluated whether kaempferol (KAM), a dietary flavonoid, offers neuroprotection in a rat BCCAO/R model. Adult Wistar rats were gavage fed a single dose of KAM (40 mg) six hours before surgery. Comprehensive lipidomic and molecular analyses were conducted on samples from the frontal and temporal-occipital cortices, as well as the plasma. In the frontal cortex, KAM elevated anti-inflammatory N-acylethanolamines palmitoylethanolamide (PEA), oleoylethanolamide (OEA), and docosahexaenoylethanolamide (DHAEA) and reduced oxidized arachidonic acid metabolites. KAM also downregulated cyclooxygenase- 2 (COX-2) protein and selectively decreased the endocannabinoid 2-arachidonoylglycerol (2-AG), showing a shift in AA metabolism. These molecular changes correlated with increased levels of peroxisome proliferator-activated receptor alpha (PPARα) and cannabinoid receptors CB1R and CB2R, supporting activation of both nuclear and membrane-bound anti-inflammatory pathways. No significant changes were observed in the temporal-occipital cortex. In plasma, DHAEA levels increased similarly to those in the cortex. However, rises in PEA and OEA were detected only in sham-operated KAM-treated animals, suggesting possible central redistribution under hypoperfusion/reperfusion stress. In summary, these findings demonstrate that KAM exerts dual anti-inflammatory effects by inhibiting COX-2-mediated prostanoid synthesis and promoting PPARα-driven lipid signaling. This dual mechanism highlights the potential of KAM as a dietary intervention to reduce neuroinflammation associated with hypoperfusion–reperfusion challenges. Full article