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The rapid mutations on hemagglutinin (HA) of influenza A virus (IAV) can lead to significant antigenic variance and consequent immune mismatch of vaccine strains. Thus, rapid antigenicity evaluation is highly desired. The subtype-specific antigenicity models have been widely used for common subtypes such as H1 and H3. However, the continuous emerging of new IAV subtypes requires the construction of universal antigenic prediction model which could be applied on multiple IAV subtypes, including the emerging or re-emerging ones. In this study, we presented Univ-Flu, series structure-based universal models for HA antigenicity prediction. Initially, the universal antigenic regions were derived on multiple subtypes. Then, a radial shell structure combined with amino acid indexes were introduced to generate the new three-dimensional structure based descriptors, which could characterize the comprehensive physical–chemical property changes between two HA variants within or across different subtypes. Further, by combining with Random Forest classifier and different training datasets, Univ-Flu could achieve high prediction performances on intra-subtype (average AUC of 0.939), inter-subtype (average AUC of 0.771), and universal-subtype (AUC of 0.978) prediction, through independent test. Results illustrated that the designed descriptor could provide accurate universal antigenic description. Finally, the application on high-throughput antigenic coverage prediction for circulating strains showed that the Univ-Flu could screen out virus strains with high cross-protective spectrum, which could provide in-silico reference for vaccine recommendation.

Abstract Baguette is a globally acclaimed bakery staple, composed by a crispy crust and soft crumb, both containing Maillard reaction products (MRPs) with potential bioactivities. However, MRPs’ impacts on the nutritional and health attributes of baguette, particularly in terms of cellular and biological functions, are yet to be clearly elucidated. This study chemically characterizes the crust and crumb of baguettes and investigates the influence of the Maillard reaction on baguette’s nutritional profile, especially in the antioxidant and anti-inflammatory effects. The findings indicate an increase in browning intensity and advanced glycation end products (AGEs) from the baguette’s interior to its exterior, alongside a significant rise in the antioxidant capacity of the crust, suggesting the Maillard reaction’s role in boosting antioxidative properties. Both the crust and crumb demonstrated strong cytocompatibility with immune cells, capable of reducing cellular oxidative stress and regulating intracellular free radical levels. The crust effectively countered peroxyl radical-induced cell membrane hyperpolarization by 91% and completely neutralized the suppression of oxygen respiration in mitochondria, displaying higher efficacy than the crumb. In contrast, crumb extracts were more potent in inhibiting lipopolysaccharide-induced expression of proinflammatory cytokines, such as interleukins-1β (IL-1β) and IL-6, in macrophages. It could provide the fundamental data and cell-based approach for investigating the biological impacts of bread on immune responses, contributing to the refinement and supplementation of nutritional recommendations.

Abstract Wine is renowned for its rich content of polyphenols, including resveratrol (Res), known for their health promoting properties. Steamed clam with wine, a popular Mediterranean delicacy that highlights the role of wine as a key ingredient. However, despite these benefits, resveratrol’s low bioavailability poses challenges. Could the process of steaming together with clam alter the digestive fate of resveratrol from wine? This study explores the potential of proteoglycan-based nanoparticles from freshwater clam (CFNPs) as a delivery vehicle for enhancing the stability and bioavailability of resveratrol, compared with wine and free Res’ solution, aiming to elucidate mechanisms facilitating Res’ absorption. The results demonstrated that CFNPs can effectively encapsulate Res with an efficiency over 70%, leading to a uniform particle size of 70.5±0.1 nm (PDI

Abstract Tumor inflammation is one of the hallmarks of tumors and is closely related to tumor occurrence and development, providing individualized prognostic prediction. However, few studies have evaluated the relationship between inflammation and the prognosis of bladder urothelial carcinoma (BLCA) patients. Therefore, we constructed a novel inflammation-related prognostic model that included six inflammation-related genes (IRGs) that can precisely predict the survival outcomes of BLCA patients. RNA-seq expression and corresponding clinical data from BLCA patients were downloaded from The Cancer Genome Atlas database. Enrichment analysis was subsequently performed to determine the enrichment of GO terms and KEGG pathways. K‒M analysis was used to compare overall survival (OS). Cox regression and LASSO regression were used to identify prognostic factors and construct the model. Finally, this prognostic model was used to evaluate cell infiltration in the BLCA tumor microenvironment and analyze the effect of immunotherapy in high- and low-risk patients. We established an IRG signature-based prognostic model with 6 IRGs (TNFRSF12A, NR1H3, ITIH4, IL1R1, ELN and CYP26B1), among which TNFRSF12A, IL1R1, ELN and CYP26B1 were unfavorable prognostic factors and NR1H3 and ITIH4 were protective indicators. High-risk score patients in the prognostic model had significantly poorer OS. Additionally, high-risk score patients were associated with an inhibitory immune tumor microenvironment and poor immunotherapy response. We also found a correlation between IRS-related genes and bladder cancer chemotherapy drugs in the drug sensitivity data. The IRG signature-based prognostic model we constructed can predict the prognosis of BLCA patients, providing additional information for individualized prognostic judgment and treatment selection.

Abstract Background The effect of SPP1 in squamous cell carcinoma of the penis (PSCC) remained unknown. We attempted to clarify the function of the SPP1 gene in PSCC. Method Eight paired penile cancer specimens (including penile cancer tissue, paracancerous tissue, and positive lymph node tissue) subjected to whole transcriptome sequencing were analysed to identify differentially expressed genes. We used immunohistochemistry to detect the expression of SPP1 protein and immune cell related proteins in penile cancer tissue. Then, we performed weighted gene coexpression network analysis (WGCNA) to identify the genes related to SPP1 in penile cancer tissue and positive lymph node tissue. Based on the GSE57955 dataset, the CIBERSORT and ssGSEA algorithms were carried out to investigate the immune environment of PSCC. GSVA analysis was conducted to identify the signaling pathways related to SPP1 subgroups. Enzyme-linked immunosorbent assay (ELISA) method was adopted to detect SPP1 level in the serum of 60 patients with penile cancer. Results Differential analysis indicated that SPP1 was the most differentially upregulated gene in both penile cancer tissues and positive lymph node tissues. Survival analysis suggested that the prognosis of the low-SPP1 group was significantly poorer than that of the high-SPP1 group. Subsequently, immune-related bioinformatics showed that SPP1 was significantly associated with B cells, CD8 + T cells, CD4 + T cells, macrophages, helper T cells, neutrophils and dendritic cells. The immunohistochemical results showed that the high-SPP1 group was characterized by relatively high expression of CD16 and relatively low expression of CD4. GSVA analysis indicated that high-SPP1 group was significantly associated with immune-related pathways such as PD-L1 expression and the PD-1 checkpoint pathway in cancer and the TNF signaling pathway. ELISA demonstrated that the serum level of SPP1 in patients with positive lymph node metastasis of penile cancer was significantly higher than that in patients with negative lymph node metastasis of penile cancer. Conclusion Our study shows that the SPP1 gene might be an effective biomarker for predicting the prognosis and the efficacy of immunotherapy in PSCC patients.

Abstract The presence and extent of regional lymph node and distant metastasis are the most fatal prognostic factors in penile squamous cell carcinoma (PSCC). However, the available biomarkers and detailed mechanisms underlying the metastasis of PSCC remain elusive. Here, we explored the expression landscape of HOX genes in twelve paired PSCC tissues, including primary tumors, metastatic lymph nodes and corresponding normal tissues, and highlighted that HOXD11 was indispensable in the progression of PSCC. HOXD11 was upregulated in PSCC cell lines and tumors, especially in metastatic lymph nodes. High HOXD11 expression was associated with aggressive features, such as advanced pN stages, extranodal extension, pelvic lymph node and distant metastasis, and predicted poor survival. Furthermore, tumorigenesis assays demonstrated that knockdown of HOXD11 not only inhibited the capability of cell proliferation, invasion and tumor growth but also reduced the burden of metastatic lymph nodes. Further mechanistic studies indicated that miR-138-5p was a tumor suppressor in PSCC by inhibiting the translation of HOXD11 post-transcriptionally through binding to the 3′ untranslated region. Furthermore, HOXD11 activated the transcription of FN1 to decompose the extracellular matrix and to promote epithelial mesenchymal transition-like phenotype metastasis via FN1/MMP2/MMP9 pathways. Our study revealed that HOXD11 is a promising prognostic biomarker and predicts advanced disease with poor outcomes, which could serve as a potential therapeutic target for PSCC.

Abstract How to maintain the physicochemical stability of oil emulsion has been one of the major challenges in food industry. Previously we reported the demulsification effects of catalase in the fish oil emulsion. In comparison, the influences of other two metal ion-containing oxidoreductases, horseradish peroxidase (HRP) and copper/zinc superoxide dismutase (SOD), on the emulsion’s stability were investigated. Submicron fish oil-in-water emulsion stabilized by polysorbate 80 was prepared by high-speed homogenization. Its physical stability was evaluated by visual and microscopic observation, turbidity and light scattering measurements, while chemical stability by the hydroperoxide content and lipid peroxidation. HRP demulsified the emulsion in a concentration-responsive manner after 3–7 days’ incubation, resulting in a decreased turbidity and significant delamination. The enlargement of oil-polysorbate droplets and protein precipitates were confirmed by size distribution and TEM observation. HRP initially elevated the emulsion’s hydroperoxide then decreased it while raising TBARS levels during 7-Day incubation. In contrary, SOD stabilized the emulsion physically and chemically. The demulsification was correspondingly attributed to the oxidation catalyzing activity of the peroxidase and the electrostatic and hydrophobic interaction between lipids and proteins. This study adds new insight to the influences of the two oxidoreductases on the stability, lipids and peroxides of food emulsions, proposes an exciting subject of elucidating the underlying mechanism.

Abstract Abundant nanostructures have been constantly found in various foods, like vinegar, tea, coffee, and milk. However, these structures largely remain unexplored and even been eliminated for stability reasons in food industry. Here we report the isolation, characterization, and antioxidant activities of food nanoparticles (NPs) carrying polyphenols from Chinese rice vinegar. Using a gel-chromatography-based isolation protocol, the vinegar was separated into three major fractions. They were identified as spherical NPs (P1), lollipop-like NPs (P2) and spherical microparticles (P3) with average hydrodynamic diameter of 210, 245,1643 nm, separately. The former two fractions accounted for the major parts of dry matter in the vinegar. The P1-NPs fraction was composed of proteins, carbohydrates, and a high number of polyphenols (15 wt%), demonstrated potent antioxidant activity as determined by ABTS and ORAC assays. Moreover, they effectively quenched peroxyl free radicals in peritoneal macrophages and promoted cellular growth. The P2 fraction contained majority of organic acids, esters and mineral elements of the vinegar. It demonstrated the NPs are bioactive units of the rice vinegar, inspiring the development of novel functional nanomaterials with nutraceutical and pharmaceutical applications.

Background: Immune checkpoint inhibitor therapy has changed the treatment model of metastatic bladder cancer. However, only approximately 20% of patients benefit from this therapy, and robust biomarkers to predict the effect of immunotherapy are still lacking. In this study, we aimed to investigate whether immune-related genes could be indicators for the prognosis of bladder cancer patients and the effect of immunotherapy.Methods: Based on bladder cancer dataset from the Cancer Genome Atlas (TCGA) and GSE48075, 22 immune microenvironment-related cells were identified by CIBERSORT. After performing a series of bioinformatic and machine learning approaches, we identified distinct tumor microenvironment clusters and three bladder cancer specific immune-related genes (EGFR, OAS1 and MST1R). Then, we constructed immune-related gene risk score (IRGRS) by using the Cox regression method and validated it with the IMvigor210 dataset.Results: IRGRS-high patients had a worse overall survival than IRGRS-low patients, which was consistent with the result in the IMvigor210 dataset. Comprehensive analysis shows that patients with high IRGRS scores are mainly enriched in basal/squamous type (Ba/Sq), and tumor metabolism-related pathways are more Active, with higher TP53 and RB1 gene mutation rates, lower CD4+/CD8+ T cell infiltration, higher M0 macrophage infiltration, and lower immunotherapy efficacy. In contrast, Patients with low IRGRS scores are mainly enriched in the luminal papillary type (LumP), which is associated with the activation of IL-17 and TNF signaling pathways, higher mutation rates of FGFR3 and CDKN1A genes, higher CD4+/CD8+ T cell infiltration content, and The level of M0 macrophage infiltration was relatively low, and the immunotherapy was more probably effective.Conclusion: Our study constructed an IRGRS for bladder cancer and clarified the immune and molecular characteristics of IRGRS-defined subgroups of bladder cancer to investigate the association between IRGRS and its potential implications for prognosis and immunotherapy.

Maillard reaction products (MRPs) of protein, amino acids, and reducing sugars from many foods and aqueous extracts of herbs are found to have various bioactivities, including antiviral effects. A hypothesis was proposed that their antiviral activity is due to the interaction with the cellular membrane. Aiming to estimate the possible actions of MRPs on phospholipid bilayers, the Arg-Glc MRPs were prepared by boiling the pre-mixed solution of arginine and glucose for 60 min at 100°C and then examined at a series of concentrations for their effects on the phase transition of MeDOPE multilamellar vesicles (MLVs), for the first time, by using differential scanning calorimetry (DSC) and temperature-resolved small-angle X-ray scattering (SAXS). Arg-Glc MRPs inhibited the lamellar gel–liquid crystal (Lβ-Lα), lamellar liquid crystal–cubic (Lα-QII), and lamellar liquid crystal–inverted hexagonal (Lα-HII) phase transitions at low concentration (molar ratio of lipid vs. MRPs was 100:1 or 100:2), but promoted all three transitions at medium concentration (100:5). At high concentration (10:1), the MRPs exhibited inhibitory effect again. The fusion peptide from simian immunodeficiency virus (SIV) induces membrane fusion by promoting the formation of a non-lamellar phase, e.g., cubic (QII) phase, and inhibiting the transition to HII. Arg-Glc MRPs, at low concentration, stabilized the lamellar structure of SIV peptide containing lipid bilayers, but facilitated the formation of non-lamellar phases at medium concentration (100:5). The concentration-dependent activity of MRPs upon lipid phase transition indiciates a potential role in modulating some membrane-related biological events, e.g., viral membrane fusion.

RAB20, a member of the RAS GTPase oncogene family, is overexpressed in several cancers with poor outcomes, promoting tumorigenesis and inducing genomic instability. Here, we performed comprehensive genomic sequencing on eight penile squamous cell carcinoma (PSCC) and normal tissue pairs and found that RAB20 was upregulated in tumors, especially in metastatic lymph nodes. RAB20 overexpression in tumors was further verified by qPCR, Western blotting, and immunohistochemistry of our newly established PSCC cell lines and paired tissues. The clinical significance of RAB20 was validated in 259 PSCC patients, the largest cohort to date, and high RAB20 expression positively correlated with the T, N, M status, extranodal extension, and clinical stage (all p < 0.01). RAB20 was an unfavorable independent prognostic indicator in the survival analysis (p = 0.011, HR = 2.090; 95% Cl: 1.183–4.692), and PSCC patients with high RAB20 expression experienced shorter 5-year cancer-specific survival times (p < 0.001). Furthermore, tumorigenesis assays demonstrated that RAB20 knockdown inhibited cell proliferation, migration, and colony formation in vitro and tumor growth in vivo. RAB20 depletion also induced PSCC cell cycle arrest at G2/M by increasing Chk1 expression and promoting cdc25c phosphorylation to reduce cdc2-cyclinB1 complex formation. Our study revealed an oncogenic role for RAB20 in promoting PSCC cell proliferation at the G2/M phase via the Chk1/cdc25c/cdc2-cyclinB1 pathway. Thus, RAB20 could be a promising prognostic biomarker of advanced PSCC with poor patient survival outcomes and could be a potential therapeutic target.