Molecular mechanism of TRIM32 in antiviral immunity in rainbow trout (Oncorhynchus mykiss).

TRIM family proteins are widely found in multicellular organisms and are involved in a wide range of life activities, and also act as crucial regulators in the antiviral natural immune response. This study aimed to reveal the molecular mechanism of rainbow trout TRIM protein in the anti-IHNV process. The results demonstrated that 99.1% homology between the rainbow trout and the chinook salmon (Oncorhynchus tshawytscha) TRIM32. When rainbow trout were infected with IHNV, the TRIM32 was highly expressed in the gill, spleen, kidney and blood. Meanwhile, rainbow trout TRIM32 has E3 ubiquitin ligase activity and undergoes K29-linked polyubiquitination modifications dependent on the RING structural domain was determined by immunoprecipitation. TRIM32 could interact with the NV protein of IHNV and degrade NV protein through the ubiquitin-proteasome pathway, and was also able to activate NF-κB transcription, thereby inhibiting the replication of IHNV. Moreover, the results of the animal studies showed that the survival rate of rainbow trout overexpressing TRIM32 was 70.2% which was significantly higher than that of the control group, and stimulating the body to produce high levels of IgM when the host was infected with the virus. In addition, TRIM32 can activate the NF-κB signalling pathway and participate in the antiviral natural immune response. The results of this study will help us to understand the molecular mechanism of TRIM protein resistance in rainbow trout, and provide new ideas for disease resistance breeding, vaccine development and immune formulation development in rainbow trout.

Interfacial engineering of Ag/C catalysts for practical electrochemical CO2 reduction to CO.

Electrochemical CO2 reduction to value-added chemicals by renewable energy sources is a promising way to implement the artificial carbon cycle. During the reaction, especially at high current densities for practical applications, the complex interaction between the key intermediates and the active sites would affect the selectivity, while the reconfiguration of electrocatalysts could restrict the stability. This paper describes the fabrication of Ag/C catalysts with a well-engineered interfacial structure, in which Ag nanoparticles are partially encapsulated by C supports. The obtained electrocatalyst exhibits CO Faradaic efficiencies (FEs) of over 90% at current densities even as high as 1.1 A/cm2. The strong interfacial interaction between Ag and C leads to highly localized electron density that promotes the rate-determining electron transfer step by enhancing the adsorption and the stabilization of the key *COO‒ intermediate. In addition, the partially encapsulated structure prevents the reconfiguration of Ag during the reaction. Stable performance for over 600 h at 500 mA/cm2 is achieved with CO FE maintaining over 95%, which is among the best stability with such a high selectivity and current density. This work provides a novel catalyst design showing the potential for the practical application of electrochemical reduction of CO2.

Identification of chemosensory genes and antennal sensilla in Nassophasis sp. (Coleoptera: Rhynchophorinae).

Phytophagous insects rely on plant volatiles to select and locate hosts for feeding or reproduction and their olfactory system is essential for detecting plant volatiles. The stem-boring pest, Nassophasis sp. damages Dendrobium and causes economic losses. Currently, there are no effective methods for its control. However, understanding the morphological and molecular basis of its olfactory system may identify new pathways for their management and control. In this study, we observed the stemborer's antennal sensilla using scanning electron microscopy, and transcriptome sequencing was undertaken to annotate and analyze its chemosensory genes. Results showed that the antennal morphology is similar between males and females, with five types of antennal sensilla observed: sensilla chaetica (SC), sensilla trichodea (ST), sensilla brush (SB), sensilla basiconica (SBA) and sensilla gemmiformium (SG). Sexual dimorphism was not observed in sensilla type, but in the length of SBA and SG. A total of 70 olfactory-related genes were annotated, including 16 odorant binding proteins (OBP), 5 chemosensory proteins (CSPs), 26 olfactory receptors (ORs), 9 gustatory receptors (GRs), 10 ionotropic receptors (IRs), and 4 sensory neuron membrane proteins (SNMPs). Most genes were highly expressed and 14 of these genes were only expressed in the head, and 7 genes in the abdomen. This study provides a theoretical basis for the olfactory perception of Nassophasis sp. and a scientific basis for developing new pest control strategies.

Determination of eleven components in rat plasma by UPLC-MS/MS and GC-MS for pharmacokinetic studies after oral administration of Citri Reticulatae Pericarpium extract.

Citri Reticulatae Pericarpium (CRP) is used as common health-care food and traditional Chinese medicine (TCM), which exerts pharmacological effects, such as anti-cardiovascular, anti-tumor, anti-oxidant, anti-inflammatory, anti-virus, hepatoprotective, blood pressure-lowering and neuroprotective. In this study, reliable, and sensitive ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) methods were developed and validated for the determination of eleven active components in rat plasma after oral administration of the CRP extract. The results of this method exhibited that the specificity, linearity (r > 0.999), precision and accuracy (the coefficient of variation (CV) < 11.5 %), recovery (52.9-107.9 %), matrix effects (63.8-107.5 %), and stability (CV < 10.8 %) met all requirements for the quantitation of plasma samples. The pharmacokinetic results showed that the Tmax of flavone glycosides was less than 0.7 h, and that of polymethoxyflavones and volatile components were within 1-7 h. Meanwhile, the area-under-the-curve (AUC) and concentration maximum (Cmax) of hesperidin, nobiletin, tangeretin, and D-limonene were higher than those of the other components, suggesting that the plasma exposure levels of these constituents were higher in CRP. The present research lays a foundation for elucidating the therapeutic material basis and provides a reference for further scientific research and clinical application of CRP.

Brilliant quantum dots' photoluminescence from a dual-resonance plasmonic grating.

Semiconductor quantum dots (QDs) have recently caused a stir as a promising and powerful lighting material applied in real-time fluorescence detection, display, and imaging. Photonic nanostructures are well suited for enhancing photoluminescence (PL) due to their ability to tailor the electromagnetic field, which raises both radiative and nonradiative decay rate of QDs nearby. However, several proposed structures with a complicated manufacturing process or low PL enhancement hinder their application and commercialization. Here, we present two kinds of dual-resonance gratings to effectively improve PL enhancement and propose a facile fabrication method based on holographic lithography. A maximum of 220-fold PL enhancement from CdSe/CdS/ZnS QDs are realized on 1D Al-coated photoresist (PR) gratings, where dual resonance bands are excited to simultaneously overlap the absorption and emission bands of QDs, much larger than those of some reported structures. Giant PL enhancement realized by cost-effective method further suggests the potential of better developing the nanostructure to QD-based optical and optoelectronic devices.

Yersinia infection induces glucose depletion and AMPK-dependent inhibition of pyroptosis in mice.

Nutritional status and pyroptosis are important for host defence against infections. However, the molecular link that integrates nutrient sensing into pyroptosis during microbial infection is unclear. Here, using metabolic profiling, we found that Yersinia pseudotuberculosis infection results in a significant decrease in intracellular glucose levels in macrophages. This leads to activation of the glucose and energy sensor AMPK, which phosphorylates the essential kinase RIPK1 at S321 during caspase-8-mediated pyroptosis. This phosphorylation inhibits RIPK1 activation and thereby restrains pyroptosis. Boosting the AMPK-RIPK1 cascade by glucose deprivation, AMPK agonists, or RIPK1-S321E knockin suppresses pyroptosis, leading to increased susceptibility to Y. pseudotuberculosis infection in mice. Ablation of AMPK in macrophages or glucose supplementation in mice is protective against infection. Thus, we reveal a molecular link between glucose sensing and pyroptosis, and unveil a mechanism by which Y. pseudotuberculosis reduces glucose levels to impact host AMPK activation and limit host pyroptosis to facilitate infection.

Development of novel monoclonal antibodies for blocking NF-κB activation induced by CD2v protein in African swine fever virus.

Background: CD2v, a critical outer envelope glycoprotein of the African swine fever virus (ASFV), plays a central role in the hemadsorption phenomenon during ASFV infection and is recognized as an essential immunoprotective protein. Monoclonal antibodies (mAbs) targeting CD2v have demonstrated promise in both diagnosing and combating African swine fever (ASF). The objective of this study was to develop specific monoclonal antibodies against CD2v. Methods: In this investigation, Recombinant CD2v was expressed in eukaryotic cells, and murine mAbs were generated through meticulous screening and hybridoma cloning. Various techniques, including indirect enzyme-linked immunosorbent assay (ELISA), western blotting, immunofluorescence assay (IFA), and bio-layer interferometry (BLI), were employed to characterize the mAbs. Epitope mapping was conducted using truncation mutants and epitope peptide mapping. Results: An optimal antibody pair for a highly sensitive sandwich ELISA was identified, and the antigenic structures recognized by the mAbs were elucidated. Two linear epitopes highly conserved in ASFV genotype II strains, particularly in Chinese endemic strains, were identified, along with a unique glycosylated epitope. Three mAbs, 2B25, 3G25, and 8G1, effectively blocked CD2v-induced NF-κB activation. Conclusions: This study provides valuable insights into the antigenic structure of ASFV CD2v. The mAbs obtained in this study hold great potential for use in the development of ASF diagnostic strategies, and the identified epitopes may contribute to vaccine development against ASFV.

Loss of ADAR1 induces ferroptosis of breast cancer cells.

Adenosine deaminases acting on RNA 1(ADAR1), an RNA editing enzyme that converts adenosine to inosine by deamination in double-stranded RNAs, plays an important role in occurrence and progression of various types of cancer. Ferroptosis has emerged as a hot topic of cancer research in recent years. We have previously reported that ADAR1 promotes breast cancer progression by regulating miR-335-5p and METTL3. However, whether ADAR1 has effects on ferroptosis in breast cancer cells is largely unknown. In this study, we knocked down ADAR1 using CRISPR-Cas9 technology or over-expressed ADAR1 protein using plasmid expressing ADAR1 in MCF-7 and MDA-MB-231 breast cancer cell lines, then detected cell viability, and levels of ROS, MDA, GSH, Fe2+, GPX4 protein and miR-335-5p. We showed that the cell proliferation was inhibited, levels of ROS, MDA, Fe2+, and miR-335-5p were increased, while GSH and GPX4 levels were decreased after loss of ADAR1, compared to the control group. The opposite effects were observed after ADAR1 overexpression in the cells. Further, we demonstrated that ADAR1-controlled miR-335-5p targeted Sp1 transcription factor of GPX4, a known ferroptosis molecular marker, leading to inhibition of ferroptosis by ADAR1 in breast cancer cells. Moreover, RNA editing activity of ADAR1 is not essential for inducing ferroptosis. Collectively, loss of ADAR1 induces ferroptosis in breast cancer cells by regulating miR-335-5p/Sp1/GPX4 pathway. The findings may provide insights into the mechanism by which ADAR1 promotes breast cancer progression via inhibiting ferroptosis.

Tadpole-Like Carbon Nanotube with Fe Nanoparticle Encapsulated at the Head and Zn Single-Atom Anchored on the Body: One-Pot Carbonization for Tetramodal Synergistic Cancer Therapy.

Precise integration of diverse therapeutic approaches into nanomaterials is the key to the development of multimodal synergistic cancer therapy. In this work, tadpole-like carbon nanotubes with Fe nanoparticle encapsulated at the head and Zn single-atom anchored on the body (Fe@CNT-Zn) is precisely designed and facilely prepared via one-pot carbonization. In vitro studies revealed the integration of chemotherapy (CT), chemodynamic therapy (CDT), photothermal therapy (PTT), and photodynamic therapy (PDT) in Fe@CNT-Zn as well as the near-infrared light (NIR)-responsive cascade therapeutic efficacy. Furthermore, in vivo studies demonstrated the NIR-triggered cascade-amplifying synergistic cancer therapy in a B16 tumor-bearing mouse model. The results not only showcased the Fe@CNT-Zn as a potential tetramodal therapeutic platform, but also demonstrated a proof-of-concept on metal-organic framework-based "one stone for multiple birds" strategy for in situ functionalization of carbon materials.

Reinforcement of the intestinal mucosal barrier via mucus-penetrating PEGylated bacteria.

The breakdown of the gut's mucosal barrier that prevents the infiltration of microorganisms, inflammatory cytokines and toxins into bodily tissues can lead to inflammatory bowel disease and to metabolic and autoimmune diseases. Here we show that the intestinal mucosal barrier can be reinforced via the oral administration of commensal bacteria coated with poly(ethylene glycol) (PEG) to facilitate their penetration into mucus. In mice with intestinal homoeostatic imbalance, mucus-penetrating PEGylated bacteria preferentially localized in mucus at the lower gastrointestinal tract, inhibited the invasion of pathogenic bacteria, maintained homoeostasis of the gut microbiota, stimulated the secretion of mucus and the expression of tight junctions, and prevented the mice from developing colitis and diabetes. Orally delivered PEGylated bacteria may help prevent and treat gastrointestinal disorders.

Genome-Wide Identification and Expression Analysis of the GRAS Gene Family and Their Responses to Heat Stress in Cymbidium goeringii.

The GRAS gene family, responsible for encoding transcription factors, serves pivotal functions in plant development, growth, and responses to stress. The exploration of the GRAS gene family within the Orchidaceae has been comparatively limited, despite its identification and functional description in various plant species. This study aimed to conduct a thorough examination of the GRAS gene family in Cymbidum goeringii, focusing on its physicochemical attributes, phylogenetic associations, gene structure, cis-acting elements, and expression profiles under heat stress. The results show that a total of 54 CgGRASs were pinpointed from the genome repository and categorized into ten subfamilies via phylogenetic associations. Assessment of gene sequence and structure disclosed the prevalent existence of the VHIID domain in most CgGRASs, with around 57.41% (31/54) CgGRASs lacking introns. The Ka/Ks ratios of all CgGRASs were below one, indicating purifying selection across all CgGRASs. Examination of cis-acting elements unveiled the presence of numerous elements linked to light response, plant hormone signaling, and stress responsiveness. Furthermore, CgGRAS5 contained the highest quantity of cis-acting elements linked to stress response. Experimental results from RT-qPCR demonstrated notable variations in the expression levels of eight CgGRASs after heat stress conditions, particularly within the LAS, HAM, and SCL4/7 subfamilies. In conclusion, this study revealed the expression pattern of CgGRASs under heat stress, providing reference for further exploration into the roles of CgGRAS transcription factors in stress adaptation.

High Apolipoprotein B/Apolipoprotein A1 is Associated with Vitamin D Deficiency Among Type 2 Diabetes Patients.

Purpose: To explore the relationship between vitamin D (VitD) deficiency and the apolipoprotein B/apolipoprotein A1 (apo B/A1) in type 2 diabetes mellitus (T2DM) patients. Methods: This was a retrospective study that lasted 2 years and 6 months, collecting information and laboratory data from 784 patients with T2DM. Patients were divided into VitD deficiency group (n = 433) and non-VitD deficiency group (n = 351) based on VitD levels. Calculated apo B/A1 ratio, and patients were further divided into high-apo B/A1 group (n = 392) and low-apo B/A1 group (n = 392) based on the median of the apo B/A1. All data were analyzed using Prism 8.0.1 and R version 4.3.1 software. Results: Apo B/A1 levels of T2DM patients combined with VitD deficiency was significantly higher than that of non-VitD deficiency patients, and the VitD levels of patients with high apo B/A1 was significantly lower than that patients with low apo B/A1 (all P<0.001). Spearman correlation analysis showed that VitD levels were negatively correlated with apo B/A1 (r=-0.238, P<0.001). Multiple linear regression analysis revealed after adjusting other factors, VitD levels were significantly negatively associated with apo B/A1 (ß=-0.123, P=0.001). Binary logistic regression analysis showed apoB/A1 was an independent risk factor for VitD deficiency in T2DM patients. Restrictive cubic spline indicated a significant linear relationship between apoB/A1 and VitD deficiency (P general trend <0.0001, P nonlinear = 0.0896), after stratification of gender, the results showed that apo B/A1 was more susceptible to VitD deficiency in female patients. The receiver operating characteristic (ROC) curve analysis showed that the area under the curve, sensitivity and specificity of the apo B/A1 for VitD deficiency were 0.654, 66.3% and 59.8%, respectively. Conclusion: The apo B/A1 was significantly negatively associated with VitD levels and an independent risk factor for VitD deficiency in patients with T2DM.

The features of male breast cancer in China: A real-world study.

BACKGROUND: Male breast cancer (MBC) is a rare disease. Although several large-scale studies have investigated MBC patients in other countries, the features of MBC patients in China have not been fully explored. This study aims to explore the features of Chinese MBC patients comprehensively. METHODS: We retrospectively collected data of MBC patients from 36 centers in China. Overall survival (OS) was evaluated by the Kaplan-Meier method, log-rank test, and Cox regression analyses. Multivariate Cox analyses were used to identify independent prognostic factors of the patients. RESULTS: In total, 1119 patients were included. The mean age at diagnosis was 60.9 years, and a significant extension over time was observed (P < 0.001). The majority of the patients (89.1 %) received mastectomy. Sentinel lymph node biopsy was performed in 7.8 % of the patients diagnosed in 2009 or earlier, and this percentage increased significantly to 38.8 % in 2020 or later (P < 0.001). The five-year OS rate for the population was 85.5 % [95 % confidence interval (CI), 82.8 %-88.4 %]. Multivariate Cox analysis identified taxane-based [T-based, hazard ratio (HR) = 0.32, 95 % CI, 0.13 to 0.78, P = 0.012] and anthracycline plus taxane-based (A + T-based, HR = 0.47, 95 % CI, 0.23 to 0.96, P = 0.037) regimens as independent protective factors for OS. However, the anthracycline-based regimen showed no significance in outcome (P = 0.175). CONCLUSION: As the most extensive MBC study in China, we described the characteristics, treatment and prognosis of Chinese MBC population comprehensively. T-based and A + T-based regimens were protective factors for OS in these patients. More research is required for this population.

MiR-143-3p regulates chondrogenic differentiation of synovium derived mesenchymal stem cells under mechanical stress through the BMPR2-Smad signalling pathway by targeting BMPR2.

BACKGROUND: Mesenchymal stem cells (MSCs) derived from the synovium, known as synovium mesenchymal stem cells (SMSCs), exhibit significant potential for articular cartilage regeneration owing to their capacity for chondrogenic differentiation. However, the microRNAs (miRNAs) governing this process and the associated mechanisms remain unclear. While mechanical stress positively influences chondrogenesis in MSCs, the miRNA-mediated response of SMSCs to mechanical stimuli is not well understood. OBJECTIVE: This study explores the miRNA-driven mechano-transduction in SMSCs chondrogenesis under mechanical stress. METHODS: The surface phenotype of SMSCs was analysed by flow cytometry. Chondrogenesis capacities of SMSCs were examined by Alcian blue staining. High throughput sequencing was used to screen mechano-sensitive miRNAs of SMSCs. The RNA expression level of COL2A1, ACAN, SOX9, BMPR2 and miR-143-3p of SMSCs were tested by quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between miR-143-3p and TLR4 was confirmed by luciferase reporter assays. The protein expression levels of related genes were assessed by western blot. RESULTS: High-throughput sequencing revealed a notable reduction in miR-143-3p levels in mechanically stressed SMSCs. Gain- or loss-of-function strategies introduced by lentivirus demonstrated that miR-143-3p overexpression hindered chondrogenic differentiation, whereas its knockdown promoted this process. Bioinformatics scrutiny and luciferase reporter assays pinpointed a potential binding site for miR-143-3p within the 3'-UTR of bone morphogenetic protein receptor type 2 (BMPR2). MiR-143-3p overexpression decreased BMPR2 expression and phosphorylated Smad1, 5 and 8 levels, while its inhibition activated BMPR2-Smad pathway. CONCLUSION: This study elucidated that miR-143-3p negatively regulates SMSCs chondrogenic differentiation through the BMPR2-Smad pathway under mechanical tensile stress. The direct targeting of BMPR2 by miR-143-3p established a novel dimension to our understanding of mechano-transduction mechanism during SMSC chondrogenesis. This understanding is crucial for advancing strategies in articular cartilage regeneration.

High performance supercapacitors deploying cube-templated tracheid cavities of wood-derived carbon.

Wood-derived carbon, with its strong tracheid array structure, is an ideal material for use as a self-supporting electrode in supercapacitors. By leveraging the inherent through pore structure and surface affinity found in wood tracheids, we successfully engineered a highly spatially efficient cube-templated porous carbon framework inside carbonized wood tracheid cavities through precise control over precursor crystallization temperatures. This innovative cubic channel architecture effectively maximizes up to (79 ± 1)% of the cavity volume in wood-derived carbon while demonstrating exceptional hydrophilicity and high conductivity properties, facilitating the development of supercapacitors with enhanced areal/volumetric capacitances (2.65F cm-2/53.0F cm-3 at 5.0 mA cm-2) as well as superior areal/volumetric energy densities (0.37 mWh cm-2/7.36 mWh cm-3 at 2.5 mW cm-2). The fabrication of these cube-templated channels with high cube filling content is not only simple and precisely controllable, but also environmentally friendly. The proposed method eliminates the conventional acid-base treatment process for pore formation, facilitating the rapid development and practical implementation of thick electrodes with superior performance in supercapacitors. Moreover, it offers a universal research approach for the commercialization of wood-derived thick electrodes.

Identification of an exosomal miRNA-mRNA regulatory network contributing to methotrexate efficacy.

OBJECTIVE: Methotrexate (MTX) is an economic and effective medicine treatment for psoriasis. Extracellular vesicle (EV) miRNA biomarkers related to its efficiency have been identified in various diseases. Whether certain miRNA profiles are associated with psoriasis treatment is unknown. In order to determine specific miRNA biomarkers for MTX effectiveness prediction and the severity of psoriasis, our study looked at the variations in circulating EV miRNA profiles before and after MTX therapy. METHODS: Plasma EV isolation and next-generation sequencing were performed to identify differentially expressed EV miRNAs between GRs (n = 14) and NRs (n = 6). Univariate and multiple linear regression analyses were performed to evaluate the correlation between PASI scores and miRNA expression levels. RESULTS: 15 miRNAs out of a total profile of 443 miRNAs were substantially different between GRs and NRs at baseline, 4 of them (miR-199a-5p, miR-195-5p, miR-196a-5p, and miR-1246) have the potential to distinguish between GRs and NRs [area under the curve (AUC) ≥ 0.70, all P < 0.05]. KEGG pathway analyses revealed differentially expressed miRNAs to potentially target immune-related pathways. SIRT1 was discovered to be a target of miR-199a-5p and involved in MAPK signaling pathway. MiR-191-5p and miR-21-5p expression levels have been discovered to positively correlate with PASI scores[P < 0.05]. CONCLUSION: This pilot investigation found that miR-199a-5p, miR-195-5p, miR-196a-5p, and miR-1246 might be prospective biomarkers to predict the efficacy of MTX, and that miR-191-5p and miR-21-5p were correlated with psoriasis severity. Five of them previously reported to be involved in MAPK signaling pathway, indicating a potential role of MTX in delaying the progression of psoriatic inflammation.

The Evolution of the WUSCHEL-Related Homeobox Gene Family in Dendrobium Species and Its Role in Sex Organ Development in D. chrysotoxum.

The WUSCHEL-related homeobox (WOX) transcription factor plays a vital role in stem cell maintenance and organ morphogenesis, which are essential processes for plant growth and development. Dendrobium chrysotoxum, D. huoshanense, and D. nobile are valued for their ornamental and medicinal properties. However, the specific functions of the WOX gene family in Dendrobium species are not well understood. In our study, a total of 30 WOX genes were present in the genomes of the three Dendrobium species (nine DchWOXs, 11 DhuWOXs, and ten DnoWOXs). These 30 WOXs were clustered into ancient clades, intermediate clades, and WUS/modern clades. All 30 WOXs contained a conserved homeodomain, and the conserved motifs and gene structures were similar among WOXs belonging to the same branch. D. chrysotoxum and D. huoshanense had one pair of fragment duplication genes and one pair of tandem duplication genes, respectively; D. nobile had two pairs of fragment duplication genes. The cis-acting regulatory elements (CREs) in the WOX promoter region were mainly enriched in the light response, stress response, and plant growth and development regulation. The expression pattern and RT-qPCR analysis revealed that the WOXs were involved in regulating the floral organ development of D. chrysotoxum. Among them, the high expression of DchWOX3 suggests that it might be involved in controlling lip development, whereas DchWOX5 might be involved in controlling ovary development. In conclusion, this work lays the groundwork for an in-depth investigation into the functions of WOX genes and their regulatory role in Dendrobium species' floral organ development.

Recent Advances in the Inhibition of Membrane Lipid Peroxidation by Food-Borne Plant Polyphenols via the Nrf2/GPx4 Pathway.

Lipid peroxidation (LP) leads to changes in the fluidity and permeability of cell membranes, affecting normal cellular function and potentially triggering apoptosis or necrosis. This process is closely correlated with the onset of many diseases. Evidence suggests that the phenolic hydroxyl groups in food-borne plant polyphenols (FPPs) make them effective antioxidants capable of preventing diseases triggered by cell membrane LP. Proper dietary intake of FPPs can attenuate cellular oxidative stress, especially damage to cell membrane phospholipids, by activating the Nrf2/GPx4 pathway. Nuclear factor E2-related factor 2 (Nrf2) is an oxidative stress antagonist. The signaling pathway regulated by Nrf2 is a defense transduction pathway of the organism against external stimuli such as reactive oxygen species and exogenous chemicals. Glutathione peroxidase 4 (GPx4), under the regulation of Nrf2, is the only enzyme that reduces cell membrane lipid peroxides with specificity, thus playing a pivotal role in regulating cellular ferroptosis and counteracting oxidative stress. This study explored the Nrf2/GPx4 pathway mechanism, antioxidant activity of FPPs, and mechanism of LP. It also highlighted the bioprotective properties of FPPs against LP and its associated mechanisms, including (i) activation of the Nrf2/GPx4 pathway, with GPx4 potentially serving as a central target protein, (ii) regulation of antioxidant enzyme activities, leading to a reduction in the production of ROS and other peroxides, and (iii) antioxidant effects on LP and downstream phospholipid structure. In conclusion, FPPs play a crucial role as natural antioxidants in preventing LP. However, further in-depth analysis of FPPs coregulation of multiple signaling pathways is required, and the combined effects of these mechanisms need further evaluation in experimental models. Human trials could provide valuable insights into new directions for research and application.

Establishment and validation of a risk score model based on EUS: assessment of lymph node metastasis in early gastric cancer.

BACKGROUND AND AIMS: Lymph node metastasis significantly affects the prognosis of early gastric cancer patients. EUS plays a crucial role in the preoperative assessment of early gastric cancer. This study evaluated the efficacy of EUS in identifying lymph node metastasis in early gastric cancer patients and developed a risk score model to aid in choosing the best treatment options. METHODS: We retrospectively analyzed the effectiveness of EUS for detecting lymph node metastasis in early gastric cancer patients. A risk score model for predicting lymph node metastasis preoperatively was created using independent risk factors identified through binary logistic regression analysis and subsequently validated. Receiver operating characteristic curves were generated for both the development and validation cohorts. RESULTS: The overall accuracy of EUS in identifying lymph node metastasis was 85.3%, although its sensitivity (29.2%) and positive predictive value (38.7%) were relatively low. Patients were categorized based on preoperative risk factors for lymph node metastasis, including tumor size of ≥20 mm, lymph nodes of ≥10 mm, body mass index of ≥24 kg/m2, and lymph node metastasis on CT scans. A 7-point risk score model was developed to assess the likelihood of lymph node metastasis. The areas under the receiver operating characteristic curve for the development and validation sets were 0.842 and 0.837, respectively, with sensitivities of 64% and 79%, respectively. CONCLUSIONS: We developed a practical risk score model based on preoperative factors to help EUS predict lymph node metastasis in early gastric cancer patients, guiding the selection of optimal treatment approaches for these patients.

Fabrication and characterization of magnetic mesoporous nanoparticles for efficient determination and magnetic separation of sulfonamides in food samples.

A magnetic, mesoporous core/shell structured Fe3O4@SiO2@mSiO2 nanocomposite was synthesized and employed as a magnetic solid phase extraction (MSPE) sorbent for the determination of trace sulfonamides (SAs) in food samples. The synthesized nanocomposite was characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis, X-ray diffraction, N2 sorption analysis and vibrating sample magnetometry. The results showed that Fe3O4@SiO2@mSiO2 possessed a mesoporous structure with a large surface area. Batch experiments were carried out to investigate the adsorption ability for SAs. Fe3O4@SiO2@mSiO2 showed fast kinetics and high adsorption capacity, and the pseudo-second-order model and Langmuir adsorption isotherm are well fitted with the experimental data, indicating that chemical adsorption might be the rate-limiting step. Moreover, the high adsorption capacity can be maintained for at least 8 runs, indicating excellent stability and reusability. The proposed method exhibited good linearity in the range of 0.2-500 µg L-1, the R2 values of all the analytes were greater than 0.99 and the LODs were all lower than 0.2 µg L-1. Furthermore, real food samples were successfully analyzed with Fe3O4@SiO2@mSiO2 and high recoveries varying from 89.7% and 110.6% were obtained with low relative standard deviations ranging from 1.78% to 6.91%. The Fe3O4@SiO2@mSiO2 magnetic nanocomposite is a promising sorbent for the efficient extraction of SAs from complex food samples.