Mechanistic Insights Research Articles

Beneficial utilization of ball-milled carbon sand to activate peroxymonosulfate oxidation: Quantitation of ROS using probe-based kinetic models and mechanism insights

In this study, the oil sand was treated with an integrated process of pyrolysis and ball milling, and the obtained ball-milled carbon sand (BMCS) was utilized as peroxymonosulfate (PMS) activator to treat wastewater containing aniline (AN). Quenching experiments and electron paramagnetic resonance (EPR) confirmed the existence of sulfate radical (SO4∙‐), hydroxyl radical (·OH) and singlet oxygen (O12) in the BMCS/PMS system. A probe-based kinetic model was constructed to describe the degradation process of pollutants in the BMCS/PMS system, quantified the exposure of each reactive oxygen species and their contributions to AN degradation. BMCS activated PMS to quickly produce SO4∙‐ and gradually generate ·OH. The O12 exposure showed a rapid increasing trend and the largest total exposure, while its contribution to AN degradation was small. Ball milling time and BMCS dosage demonstrated significant effect on the exposure of ·OH and O12. The main active sites for BMCS to activate PMS were iron oxides, defective carbon and oxygen-containing functional groups. This study provides a green and low-cost process for value-added transformation of pyrolytic residue of oil sand (PROS), so as to promote PROS treatment mode from harmless disposal to resource utilization.

The Rac1-PAK1-Arp2/3 signaling axis regulates CHIKV nsP1-induced filopodia and optimal viral genome replication

ABSTRACT Alphavirus infection induces dramatic remodeling of host cellular membranes, producing filopodia-like and intercellular extensions. The formation of filopodia-like extensions has been primarily assigned to the replication protein nsP1, which binds and reshapes the host plasma membrane when expressed alone. While reported decades ago, the molecular mechanisms behind nsP1 membrane deformation remain unknown. Using mammalian epithelial cells and Chikungunya virus (CHIKV) as models, we characterized nsP1-induced membrane deformations as highly dynamic actin-rich lamellipodia and filopodia-like extensions. Through pharmacological inhibition and genetic invalidation, we identified the critical contribution of the Rac1 GTPase and its downstream effectors PAK1 and the actin nucleator Arp2 in nsP1-induced membrane deformation. An intact Rac1-PAK1-Arp2 signaling axis was also required for optimal CHIKV genome replication. Therefore, our results designate the Rac1-PAK1-Arp2 pathway as an essential signaling node for CHIKV infection and establish a parallel requirement for host factors involved in nsP1-induced plasma membrane reshaping and assembly of a functional replication complex. IMPORTANCE The alphavirus nsP1 protein dramatically remodels host cellular membranes, resulting in the formation of filopodia-like extensions. Although described decades ago, the molecular mechanisms controlling these membrane deformations and their functional importance remain elusive. Our study provides mechanistic insight, uncovering the critical role of the Rac1 GTPase, along with its downstream effectors PAK1 and the actin nucleator Arp2, in the nsP1-associated phenotype. Furthermore, we demonstrate that the Rac1-PAK1-Arp2 pathway is essential for optimal CHIKV genome replication. Our findings establish a parallel in the cellular mechanisms governing nsP1-induced plasma membrane reshaping and the production of a functional replication complex in infected cells.

Mechanistic Insights into CO Reactivity on Iron-Based Catalysts: Role of Surface Atomic Carbon

Mechanistic Insights into CO Reactivity on Iron-Based Catalysts: Role of Surface Atomic Carbon

Biosynthesis of mechanically recyclable 3D-Cu2O@megacatalyst for Fenton-like catalysis of tetracycline and the mechanistic insights

Treating sewage waters contaminated with persistent organic pollutants (POPs) presents a pressing environmental concern, mandating, affordable, implementable and sustainable remediations. Supported catalysts, wherein metal nanoparticles are grafted onto inert supports to endow porosity, reactant access, performance and catalyst re-use are emerging as sustainable catalytic platforms. Herein, size-controllable, mechanically recyclable 3D-Cu2O@megacatalyst of ∼81 ± 5 cm2, ∼37 ± 3 cm2 and ∼1 ± 0.6 cm2 were biofabricated by exploiting the innate metal binding feature of pristine eggshells. The as-fabricated Cu2O@megacatalyst was utilized for the Fenton-like treatment of POPs, with exceptional activities against diverse molecules: antibiotic (tetracycline (TC)), textile dye (methylene blue) and pharmaceutical precursor (4-nitrophenol) with the degradation efficiencies of 95.6 %, 96.8 % and 93.4 %, respectively. Optimization studies revealed that our megacatalyst can function consistently in the presence of various oxidising agents, free radical scavengers, wide pH, temperatures and inorganic and organic contaminants. The catalyst demonstrated stability and catalytic efficiency in different real-time water matrices: ultrapure water-95.6 %, tap water-84 %, lake water-86 %, and river water-91 %. Furthermore, plausible reaction mechanism and decomposition pathways for TC degradation were assessed using GC-MS, while evaluating the toxicity using ECOSAR and oxygen uptake assay, which revealed less toxic reaction intermediates and end products. Overall, our results provide new insight into the sustainable development of a generalized highly stable, scalable, ultra-efficient and mechanically recyclable Fenton-like supported catalyst for the detoxification of POPs in sewage waters.

Baicalin Attenuates Type 2 Immune Responses in a Mouse Allergic Asthma Model through Inhibiting the Production of Thymic Stromal Lymphopoietin

Plain Language SummaryBaicalin is a flavonoid chemical extracted and purified from Scutellaria baicalensis Georgi, which possesses broad pharmacological properties. Our work objected to explore the protective effect of baicalin on allergic asthma and the possible mechanisms on regulating type 2 immune response. Mice were stimulated with OVA and administrated with baicalin. We found that eosinophils infiltrate in BALF were reduced remarkably in baicalin-treated asthmatic mice. Baicalin decreased OVA-induced inflammatory cytokines and serum immunoglobulin E secretion significantly. Moreover, baicalin alleviated the asthmatic pathological changes and substantially suppressed TSLP expression in the lung tissues. Our study indicates that baicalin attenuates OVA-induced allergic asthma in mice effectively by suppressing type 2 immune responses, which may provide a new mechanistic insight into the anti-asthmatic activity of baicalin.

Surface and electrochemical characteristics of S-scheme nanoheterostructured photocatalysts of AgIO3/Cu2SnS3 with enhanced solar energy driven photocatalytic activity

Wastewater treatment is regarded as one of the most challenges to overcome worldwide water threats. As a result, great efforts were devoted to find alterative solutions to maximize the usage of wastewater in industries or agriculture which consumes 70 % of water resources. Interestingly, the utilization of solar energy as a renewable, green and costless energy source is the ideal sustainable solution for wastewater treatment. In this context, Chalcogenides based nanoheterostructures such as AgIO3/Cu2SnS3 were prepared via simple, cost-effective and large-scale methods then utilized as visible light active photocatalysts for wastewater treatment. Scanning electron microscopy (SEM), X-ray powder diffraction (XRD), N2 sorpometry (BET), X-ray photoelectron spectroscopy (XPS), ultraviolet visible light spectrophotometry (UV–vis), and Isoelectric point (pHiep) were utilized to investigate the characteristics of nanoheterostructures. The produced nanoheterostructures were evaluated as photocatalysts for amoxicillin photodegradation using solar energy. The AgIO3/Cu2SnS3 (25ACS) demonstrated a superior photodegradation efficiency (93.5 %) after 60 min. Mot-Schottky plots and trapping experiments were carried out to have an extensive insight of the photodegradation mechanism.

Multiple intermediates in the detergent-induced fusion of lipid vesicles

Detergent-induced vesicle interactions, critical for applications including virus inactivation, varies according to the detergent type and membrane composition, but the underlying mechanistic details remain underexplored. Here, we use a lipid mixing assay based on Förster resonance energy transfer (FRET), and single-vesicle characterization approaches to identify that sub-micron-sized vesicles are induced to fuse by the non-ionic detergent Triton-X-100. We demonstrate that the process is a multi-step mechanism, characterized by discrete values of FRET efficiency between membrane-embedded fluorophores, and involves permeabilization, vesicle docking, hemi-fusion and full lipid mixing at sub-solubilizing detergent concentrations. We also dissect the kinetics of vesicle fusion to surface-tethered vesicles using a label-free quartz-crystal microbalance with dissipation monitoring approach, opening a platform for biotechnology applications. The presented strategies provide mechanistic insight into the dynamics of vesicle fusion and have implications for applications including drug delivery and sensor development where transport and manipulation of encapsulated cargo is essential.

Exploring Astaxanthin-Loaded Nanoformulations for Skin Targeting: Present Progress and Prospective Directions

This comprehensive review provides information on astaxanthin-loaded topical nanocarrier- based formulations for targeted skin enhancement. Astaxanthin, a potent carotenoid derived from microalgae, has garnered considerable attention for its multifaceted potential in skincare, particularly when incorporated into nanocarriers. These nanocarriers, like nanoemulsions, micelles, hydrogels and nanoparticles, have revolutionized the field of dermatology by providing innovative solutions to overcome the limitations associated with astaxanthin's solubility and stability. Astaxanthin's exceptional antioxidant properties, including its ability to neutralize free radicals within both lipid and aqueous environments, make it a compelling bioactive ingredient for combatting oxidative stress, a central contributor to skin aging and various dermatological conditions. The nanoscale size of these carriers facilitates enhanced skin penetration, controlled release, and improved bioavailability, thereby augmenting astaxanthin's therapeutic efficacy. This review meticulously explores the mechanistic insights behind astaxanthin's enhanced delivery and its multifaceted benefits, including photoprotection, anti-inflammatory effects, and wound healing properties. The diverse applications of astaxanthin-loaded nanocarriers in skincare, spanning anti-aging formulations, UV protection, scar healing, and wound repair, are elucidated. Safety considerations are also addressed, drawing from an extensive analysis of preclinical and clinical studies. The review provides valuable insights into optimal concentrations, formulation strategies, and regulatory aspects governing astaxanthin-loaded nanocarriers in skincare products.

Egfl6 promotes ovarian cancer progression by enhancing the immunosuppressive functions of tumor-associated myeloid cells.

Tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) play a critical role in resistance to immunotherapy. In this study, we identified epidermal growth factor-like 6 (Egfl6) as a new regulator of myeloid cell functions. Our analyses indicated that Egfl6, via binding with β3 integrins and activation of p38 and SYK signaling, acts as a chemotactic factor for myeloid cells migration and promotes their differentiation towards an immunosuppressive state. In syngeneic mouse models of ovarian cancer (OvCa), tumor expression of Egfl6 increased the intra-tumoral accumulation of polymorphonuclear (PMN) MDSCs and TAMs and their expression of immunosuppressive factors, including CXCL2, IL-10 and PD-L1. Consistent with this, in an immune 'hot' tumor model, Egfl6 expression eliminated response to a-PD-L1 therapy, while Egfl6 neutralizing antibody decreased the accumulation of tumor-infiltrating CD206+ TAMs and PMN-MDSCs and restored the efficacy of a-PD-L1 therapy. Supporting a role in human tumors, in human OvCa tissue samples, areas of high EGFL6 expression co-localized with myeloid cell infiltration. scRNAseq analyses revealed a correlation between EGFL6 and immune cell expression of immunosuppressive factors. Our data provide mechanistic insights into the onco-immunologic functions of EGFL6 in mediating tumor immune suppression and identified EGFL6 as a potential novel therapeutic target to enhance immunotherapy in OvCa patients.

UBE2T promotes stage I lung adenocarcinoma progression through PBX1 ubiquitination and PBX1/RORA regulation

BackgroundPost-translational modification pathway of protein ubiquitination is intricately associated with tumorigenesis. We previously reported elevated ubiquitin-conjugating enzyme 2T (UBE2T) as an independent risk factor in stage I lung adenocarcinoma and promoting cellular proliferation. However, its underlying mechanisms needed further investigation.MethodsImmunohistochemistry was used to assess the expression of UBE2T and retinoic acid receptor-related orphan receptor α (RORA) in stage I LUAD. Cell proliferation, migration, and invasion of LUAD cell lines were measured by Cell Counting Kit-8 assay (CCK-8), Colony-forming assay and Transwell assay, respectively. Western blot analysis was performed to determine the expression of epithelial-mesenchymal transition (EMT) markers. A xenograft model was established to evaluate the proliferative capacity of UBE2T and its interaction with RORA in promoting LUAD. Mechanistic insights into the promotion of early-stage LUAD by UBE2T were obtained through luciferase reporter assay, chromatin immunoprecipitation and co-immunoprecipitation.ResultsUBE2T and RORA expression was significantly up- and down-regulated in early-stage LUAD patients which’s proved to be associated with unfavorable outcomes, strengthened cell proliferation, migration, EMT and invasion through its interaction with RORA both in vivo and in vitro. The growth NSCLC xenografts was reduced by down-expression of UBE2T but was suppressed by RORA knockout. Mechanistically, UBE2T mediated the ubiquitination of the intermediate transcription factor PBX1, which played a transcriptional role in downstream regulation of RORA.ConclusionThe oncogenic role of UBE2T and the UBE2T-PBX1-RORA axis in driving malignant progression in Stage I LUAD had been established. UBE2T might be a novel and promising therapeutic target for LUAD treatment.

Dual-Metal-Site Metal-Organic Frameworks for Oxygen Reduction: The Crucial Role of Environmental Species Covering on the Secondary Site.

Macrocycle-based dual-metal-site metal-organic frameworks emerge as promising catalysts whose activity can be conveniently manipulated via metal node modification. However, how the metal node affects catalysis remains unclear. Herein, using first-principles calculations, we provide new mechanistic insight into dual-metal-site catalysis, where the recently synthesized M1-CoOAPc materials (M1 = Co, Ni, Cu; OAPc = octaaminophthalocyanine) are adopted for demonstration. The modeling results explain experimental measurements of Ni- and Cu-CoOAPc for facilitating oxygen reduction while highlighting a contradiction between the theoretical and experimental activity of Co-CoOAPc. Remarkably, this contradiction is attributed to the inherent H2O adsorption on Co nodes, which is usually neglected in dual-metal-site studies. We expand M1-CoOAPc with other metal nodes and find that Fe-CoOAPc (involving *H2O on the Fe nodes) exhibits a desirable theoretical half-wave potential of 0.82 V, as revealed from constant-potential and microkinetic modeling. This work improves the understanding of dual-metal-site catalysis by uncovering the impact of environmental species covering on the secondary site.

Mechanistic insights into the pyrolysis of pine resin sludge based on experiments and ReaxFF-MD simulation: High-value bio-oil production, nitrogen conversion, kinetics and environmental risk assessment

Forestry and agro-industrial waste conversion into high-value chemicals and fuels is considered one of the hottest ongoing research and industrial topics toward sustainable development. As one of the forestry and agro-industrial waste, pine resin sludge (PRS) with amino acids, pine resin residues and their derivatives such as abietic acid and 4-Epidehydroabietal, have ecological toxicity and require environmentally friendly treatment. Herein, a thermal process of PRS that generates high-value biofuels while reducing environmental pollution was reported. The results of the experiment and simulation reveal that the N of bio-oil is the major evolution direction of N, and the nitrogenous gas product is mainly NH3, a useful synthesis gas. ReaxFF-MD simulations elucidated the migration and conversion mechanism of nitrogen in amino acids. The main products of amino acid pyrolysis are 3-oxo-2-Propenenitrile, 2,4-Cyclopentadien-1-ylidenemethanone and 4R)-4-amino-5,5-dihydroxypentanoic acid. PRS's thermal weightlessness was divided into three phases, and the average activation under non-isothermal conditions was calculated at 78.17, 85.68, 206.42 kJ/mol (thermal decomposition) and final 117.78, 149.31, 195.54 kJ/mol (thermal oxidation). Thermal decomposition and oxidation process followed Avrami-Erofeev model (n=2), three-dimensional diffusion model (n=3) and mampel power (n=1). PY-GC/MS analysis shows that pyrolysis at different temperatures recovered mainly 4-Epidehydroabietal (37.15–89.67 %) for potential use as the biosynthesis of dehydrofolate. The bio-oil from PRS pyrolysis shows an excellent yield (31.43 %) and a high calorific value (37.21 MJ/kg), which is comparable to biodiesel. This work focused on offering an appealing and instructive guide for the logical treatment of sludge from pine resin production.

Mechanistic Insight into Anticancer Prowess of Piper Species and their Bioactive Compounds: A Review

Southern Asia boasts a diverse array of Piper species, renowned for their antimicrobial, antioxidant, and anti-inflammatory properties. These plants, also native to the American tropics, have played a significant role in traditional medicine and culinary practices. Notably, Piper longum L., P. nigrum L., and P. betle L. are recognized for their bioactive compounds, particularly alkaloids, which contribute to their beneficial properties. In recent decades, there has been increased focus on studying these plants for their potential anticancer effects, encompassing both direct cytotoxic effects and indirect modulation of the tumor microenvironment. Major scientific literature databases were consulted using appropriate keywords to present a comprehensive and proportionate analysis of the anticancer potential of the three species, including valuable insights into their therapeutic perspectives, molecular mechanisms, and broader applications in cancer treatment. Numerous pharmacological trials on the bioactive components and extracts have underscored their clinical significance, revealing multifaceted actions such as antiproliferative effects, antiangiogenic properties, immunomodulation, antimetastatic activity, induction of apoptosis, and modulation of various signaling pathways in both malignant and non-malignant disorders. Among the explored compounds, piperine and piperlongumine, prominent alkaloids within the Piper genus, have demonstrated notable efficacy in restricting the growth of cancer cells and tumors. This article emphasizes the biomedical and pharmacological findings related to the anticancer properties of the three Piper species, with a focus on their mechanism of action. These insights could open avenues for future clinical scenarios and therapeutic utilization of bioactive substances and extracts derived from these species.

Clinical complications in envenoming by Apis honeybee stings: insights into mechanisms, diagnosis, and pharmacological interventions.

Envenoming resulting from Apis honeybee stings pose a neglected public health concern, with clinical complications ranging from mild local reactions to severe systemic manifestations. This review explores the mechanisms underlying envenoming by honeybee sting, discusses diagnostic approaches, and reviews current pharmacological interventions. This section explores the diverse clinical presentations of honeybee envenoming, including allergic and non-allergic reactions, emphasizing the need for accurate diagnosis to guide appropriate medical management. Mechanistic insights into the honeybee venom's impact on physiological systems, including the immune and cardiovascular systems, are provided to enhance understanding of the complexities of honeybee sting envenoming. Additionally, the article evaluates emerging diagnostic technologies and therapeutic strategies, providing a critical analysis of their potential contributions to improved patient outcomes. This article aims to provide current knowledge for healthcare professionals to effectively manage honeybee sting envenoming, thereby improving patient care and treatment outcomes.

Synthesis, Molecular Docking, and Anticancer Screening of Ester-based Thiazole Derivatives.

This study investigates the potential of five compounds as novel anticancer agents. We examined their efficacy, mechanisms of action, and impact on various cancer cell lines, through a comprehensive set of experiments. Notably, compound 3e demonstrated superior activity compared to the positive control cisplatin, with a GI50 value of 6.3±0.7 μM against the breast cancer cell line (MCF-7). Compound 3b also displayed remarkable growth inhibition, yielding GI50 values of 8.7±0.2 μM (MCF-7) and 8.9±0.5 μM against the colon cancer cell line (HCT-116). Cell count experiments further confirmed the potent inhibitory effects of compounds 3e, 3b, and 3c on MCF-7 and HCT-116 cell growth. Compound 3e demonstrated a reduction of 55-60 % at GI50 and complete inhibition (100 %) at 2x GI50. Compound 3b exhibited 50-55 % reduction (GI50) and 90-95 % inhibition (2x GI50) in HCT-116 cells. Compound 3c displayed 75-80 % inhibition (2x GI50) and 35-40 % inhibition (GI50) in HCT-116 cells. In-depth mechanistic investigations unveiled valuable insights into the mode of action of compound 3e. The cell-cycle assay demonstrated G2/M phase arrest, DNA damage, and caspase-mediated apoptosis in both MCF-7 and HCT-116 cells. Caspase activation indicated a significant increase in apoptosis following exposure to compound 3e. Furthermore, compound 3e induced reactive oxygen species (ROS) production, influencing HCT-116 and MCF-7 cells differently. Elevated ROS production in HCT-116 cells and distinct effects in MCF-7 cells contribute to a deeper understanding of the cytotoxic mechanisms of compound 3e. Overall, these findings highlight the potential of the investigated compounds, particularly compound 3e, as effective inducers of apoptosis in cancer cells. Mechanistic insights into cell cycle arrest, caspase-mediated apoptosis, and ROS modulation provide a comprehensive understanding of their cytotoxic effects. This study offers significant contribution to the development of promising anticancer agents and their therapeutic applications.

1H NMR chemometrics and mechanistic insights on the thermal degradation of coconut oil

AbstractThe re‐use and prolonged heating of cooking oils is a common practice in preparing deep‐fried foods. However, this could be unsafe and pose a health threat to consumers. This work investigates the thermal degradation of edible coconut oil under prolonged heating using chemometrics analysis of proton nuclear magnetic resonance (1H NMR) data. Coconut oil samples were heated continuously without food matrix at three different temperatures (150, 175, and 200°C) for 12 h and the 1H NMR spectra were collected every hour. NMR data revealed the formation of aldehyde oxidation products. Partial least squares discriminant analysis (PLS‐DA) discriminated the samples based on temperature and heating time. The Variable Importance Projection revealed the discriminating peaks highlighting the spectral feature due to hydroperoxides and aldehydes in the oil degradation. A probe into the 1H NMR of the degradation products of saturated coconut oil confirmed the formation of a ketone as evidenced by a CH2 triplet in the chemical shift region of protons alpha to a ketone. The results showed that the thermal degradation of coconut oil was influenced by temperature, time, moisture, and oxygen in the air which can contribute to the advancement in the control and assessment of coconut oil quality.

Enhanced efficiency of manganese molecular sieves through K2FeO4 and KMnO4 modification: optimization and mechanistic insights

Enhanced efficiency of manganese molecular sieves through K2FeO4 and KMnO4 modification: optimization and mechanistic insights

Exome wide association study for blood lipids in 1,158,017 individuals from diverse populations.

Rare coding alleles play crucial roles in the molecular diagnosis of genetic diseases. However, the systemic identification of these alleles has been challenging due to their scarcity in the general population. Here, we discovered and characterized rare coding alleles contributing to genetic dyslipidemia, a principal risk for coronary artery disease, among over a million individuals combining three large contemporary genetic datasets (the Million Veteran Program, n = 634,535, UK Biobank, n = 431,178, and the All of Us Research Program, n = 92,304) totaling 1,158,017 multi-ancestral individuals. Unlike previous rare variant studies in lipids, this study included 238,243 individuals (20.6%) from non-European-like populations. Testing 2,997,401 rare coding variants from diverse backgrounds, we identified 800 exome-wide significant associations across 209 genes including 176 predicted loss of function and 624 missense variants. Among these exome-wide associations, 130 associations were driven by non-European-like populations. Associated alleles are highly enriched in functional variant classes, showed significant additive and recessive associations, exhibited similar effects across populations, and resolved pathogenicity for variants enriched in African or South-Asian populations. Furthermore, we identified 5 lipid-related genes associated with coronary artery disease (RORC, CFAP65, GTF2E2, PLCB3, and ZNF117) . Among them, RORC is a potentially novel therapeutic target through the down regulation of LDLC by its silencing. This study provides resources and insights for understanding causal mechanisms, quantifying the expressivity of rare coding alleles, and identifying novel drug targets across diverse populations.

C-FOS inhibition promotes pancreatic cancer cell ferroptosis by transcriptionally regulating the expression of SLC7A11.

Cellular proto-oncogene C-Fos forms the AP-1 transcription factor by dimerizing with proto-oncogene c-Jun; this factor upregulates the transcription of genes associated with different malignancies. However, its functions in pancreatic adenocarcinoma (PAAD) remain poorly understood. In this study, the c-Fos was increased in PAAD cells and tissues through bioinformatic analysis, RT-PCR, and WB. In two PAAD cell lines, PANC-1 and BxPC-3, we performed c-Fos knockdown studies using short hairpin RNA (shRNA). Functional analysis indicated that c-Fos depletion in PAAD cells inhibits cell proliferation and promotes ferroptosis. Chromatin Immunoprecipitation (ChIP) and Dual-luciferase experiments showed that c-Fos coupled to the promoter region of SLC7A11 stimulated its transcription, providing mechanistic insight into the process. Moreover, SLC7A11 blocked the decline of proliferation and ferroptosis by c-Fos knockdown in PAAD cells. Furthermore, a xenograft nude mouse model was established to study the impact of c-Fos on tumorigenesis in vivo. Depletion of c-Fos could suppress PC tumor growth and the expressions of SLC7A11, ki-67, and 4HNE, but overexpression of SLC7A11 reversed this process. In summary, our investigation has shown that c-Fos acts as a transcriptional regulator of SLC7A11, which may enhance tumour growth in pancreatic cancer by inhibiting ferroptosis. These results indicate that c-Fos might be a promising target for treating ferroptosis in PAAD.

The influence of Quercetin on behavior, performance and splenic immunity in broiler chickens

Quercetin (QRT), a potent flavonoid, holds immense mechanistic potential in enhancing various aspects of broiler chicken physiological status. This comprehensive study explores the profound еffеcts of QRT on behavior, productive performance, and immune functions, unraveling the underlying mechanisms behind its efficacy. Four hundred, one-day-old Cobb 500 chicks were placed randomly into 4 supplementation groups (100 birds /group and five replicates) and provided diets enriched with varying concentrations of QRT (0, 200, 400, and 600 ppm) for six weeks. Visual scanning revealed significant (P > 0.05) improvements in feeding and body care behaviors, accompanied by reduced instances of idleness and walking in the QRT-supplemented groups. Moreover, QRT supplementation exerted a substantial (P > 0.05) positive influence on weight gain, feed intake and the final body weight of the broilers. In-depth evaluation of immune parameters, QRT supplementation elicited significant (P > 0.05) enhancements in immune functions, including improved spleen, thymus, and bursa indices, enhanced secretion of immunoglobulin M (IgM) and immunoglobulin A (IgA), and stimulated humoral immunity against sheep red blood cells (SRBCs). Furthermore, QRT displays potent antioxidant properties, as showed by diminished splenic malondialdehyde levels and augmented activity of antioxidative stress enzymes. Remarkably, QRT supplementation elicited dose-dependent upregulation (P < 0.001) of key immune-related genes, such as intеrlеukin-4 (IL-4), interferon-γ (INF-γ), Toll-like receptor 2 (TLR2), and tumor necrosis factor-α (TNF-α) in the splenic tissue. Collectively, these mechanistic insights underscore the profound impact of QRT as a functional feed additive, fostering enhanced behavior, performance, and immune function in broiler chickens, while delivering robust antioxidant fortification.