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Abstract Cyanidin‐3‐O‐glucoside (C3G), an abundant and widely utilized anthocyanin monomer, has been shown to significantly inhibit cholesterol absorption. Building on our previous research demonstrating the role of Lactobacillus as a specific intestinal microflora associated with C3G‐mediated cholesterol absorption inhibition, the present study aimed to evaluate the inhibitory effects of C3G on high‐fat diet–induced cholesterol absorption. Results indicate that C3G significantly reduced total cholesterol and triglyceride levels while suppressing red grease formation in Caco‐2 cells. In vivo, C3G ameliorated blood lipid levels and mitigated small intestinal damage, as evidenced by restored villus length and basal thickness. Additionally, C3G upregulated intestinal farnesoid X receptor (FXR) mRNA expression and inhibited the expression of key cholesterol absorption proteins, Niemann‐Pick C1‐Like 1 and acetyl‐CoA acetyltransferase 2. Furthermore, C3G increased short‐chain fatty acid content and activated ileal bile acid‐binding protein expression. C3G also inhibited intestinal bile acid (BA) reabsorption, promoted fecal BA excretion, and obstructed cholesterol emulsification. Moreover, C3G modulated gut microbiota abundance and diversity, increasing the abundance of Akkermansia, Bifidobacterium, Coprococcus, Ruminococcus, and Butyricicoccus. In conclusion, our findings suggest that C3G inhibits cholesterol absorption by reshaping intestinal flora composition and regulating the FXR‐BAs axis. This study provides a theoretical foundation for the use of C3G as a raw material for inhibiting cholesterol absorption.

This study compared the taste and nutrition related metabolites of wild blueberry (WB) and cultivated blueberry (CB) varieties in Northeast China based on widely targeted metabolomics. A total of 858 metabolites were identified, of which 254 showed significant differences. 16 carbohydrates were significantly higher in CBs than in WB, while 11 organic acids were the opposite. Otherwise, 24 flavonoids have significant advantages in WB, while amino acids and their derivatives have specific advantages in WB and CBs, which may determine the differences in fruit aroma and taste between the two. In addition, we found that “alanine, aspartate, and glutamate metabolism” is the most critical differential metabolic pathway among WB and CBs; fumaric acid, succinic acid, L-glutamic acid, and L-argininosuccinate are considered key biomarkers for distinguishing WB from CBs. This study will provide a reference for Chinese blueberries' scientific introduction of seeds, comprehensive development and effective differentiation of related products.

BackgroundUCK2 (Uridine-Cytidine Kinase 2) is a promising prognostic marker for malignant tumors, but its association with immune infiltration and cancer stemness in pan-cancer remains to be fully understood. we find that gene UCK2 is closed related to RNA stemness scores (RNAss) and DNA stemness scores (DNAss), which is measured the tumor stemness. We also discover an association between UCK2 expression and immune cells by CIBERSORT algorithm, ESTIMATE algorithm and ssGSEA algorithm, especially, related to T cell, monocytes, mast cells, and macrophages. This study aims to shed light on the role and possible mechanism of UCK2 in pan-cancer.MethodsWe used the R programming language for pan-cancer bulk sequencing data analysis, which were obtained from the University of California, Santa Cruz (UCSC) datasets. UCSC database is a very useful for explore data from TCGA and other cancer genomics datasets, The data we explored at the UCK2 transcriptome level came from TCGA data in the UCSC database. We explored differential UCK2 expression between tumor and normal samples. Immunohistochemistry (IHC) was utilized to validate the expression of UCK2 in different types cancers using tumor tissue chips. The correlations of UCK2 with prognosis, genetic instability, DNA repair, cancer stem cell characteristics, and immune cell infiltration were investigated. Furthermore, single-cell datasets, acquired from the Gene Expression Omnibus (GEO) database, were used to validate the relationship between UCK2 and immune cells. GEO is a famous public genomics database supporting freely disseminates microarray data. Finally, we analyzed the correlation between UCK2 and drug sensitivity.ResultsUCK2 expression was observed to be high in most cancers and was remarkably related to the prognosis of pan-cancers. We found that the increased UCK2 expression was associated with higher genetic instability. Additionally, positive relationships were observed between UCK2 expression and mismatch repair genes, homologous recombination repair genes, and cancer stemness across different cancer types. There were significant correlations between UCK2 and T cells, monocytes, mast cells, and macrophages. Moreover, as expected, the immune checkpoint human leucocyte antigen (HLA) was found to be negatively related to UCK2. Similarly, UCK2 was also observed to have a negative association with major histocompatibility complex (MHC) genes. We noted that UCK2 had significant correlations with the sensitivity to various anti-cancer drug.ConclusionWe have observed that UCK2 plays pivotal roles in prognosis and tumor immunity, and it is associated with DNA repair and cancer stemness. The UCK2 gene exhibits a strong correlation with the immune checkpoints HLA. This study highlights its potential impact on drug sensitivity.

Abstract The TBS is a new method for clinicians to assess the bone quality. It is directly related to the mechanical strength of bone and helps predict fracture risk. The present analysis aimed to investigate the associations between serum PTH levels and TBS by analyzing data from the National Health and Nutrition Examination Survey (NHANES). A total of 3516 participants from the NHANES 2005–2006 were included in this cross-sectional study. The independent variable was serum PTH, and the outcome variable was TBS. The associations of serum PTH levels with TBS were examined using multivariable linear regression models. After adjusting for covariates, there was a negative association between serum PTH level and TBS (β = − 0.0034; 95% confidence interval, − 0.0050 to − 0.0017). However, in the subgroup analysis stratified by gender, race, and age, this association became negative only in Non-Hispanic White (β = − 0.0047, 95% CI: − 0.0071 to − 0.0048) and young people (age

Constipation is a common intestinal disease. Kiwi berries can effectively prevent constipation. However, studies have yet to be done to determine how kiwi berries prevent constipation. For two weeks, mice in this study were continually orally gavaged with kiwi berry, loperamide, or a combination of the 2. This study found that the kiwi group’s feces had more water than the constipated mice. In addition, kiwi berries can speed up gastrointestinal transit (GI), shorten the time it takes to pass the first dark stool, and dramatically enhance body weight gain. In the interstitial cells of Cajal (ICC) cells and colon tissues, alterations in the protein expression of vasoactive intestinal peptide (VIP), cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), and aquaporin-3 (AQP3) were found. At 3, 6, and 12 h of ICC cells and mouse colon, the kiwi group’s VIP, cAMP, PKA, and AQP3 protein expression levels were lower than those of the constipated mice. The kiwi berry can decrease the Firmicutes to Bacteroidetes ratio and boost the diversity and quantity of gut microbiota. By inf luencing the gut microbiota and VIP-cAMP-PKA-AQP3 signaling pathway, kiwi berries prevent constipation.

The black chokeberry is rich in polyphenols, including flavonoids with anthocyanins, flavanols and f lavonols as the main components and a variety of phenolic acids represented by chlorogenic acid. Because of these polyphenols, black chokeberry has the effect of preventing and adjuvant therapy diseases. This study summarized the current research results on the types and contents of functional components in black chokeberry, and analyzed their digestion, absorption and metabolism in human body. On this basis, the disease control functions that have been proved effective in clinical research were reviewed and analyzed. These studies showed that black chokeberry have good prevention and adjuvant therapy effects on hyperlipidemia,hypertension, diabetes and inflammation. Because there are different functional components in black chokeberry, its prevention and treatment of the same disease can come from multiple pathways, which provides a more reliable effectiveness for the disease control of different populations.

Introduction Osteoarthritis of the hip or knee has been reported to be linked to an increased risk of frailty. However, a definitive conclusion about whether hip or knee osteoarthritis increases susceptibility to frailty remains elusive. Material and methods The instrumental variables (IVs) used in this analysis were sourced from publicly available genome-wide association study (GWAS) datasets. We used a two-sample Mendelian randomization analysis to evaluate the plausible causal nexus between hip or knee osteoarthritis and frailty. Results We included a total of 25 single-nucleotide polymorphisms (SNPs) as instrumental variables through rigorous and comprehensive screening. The results of this analysis suggested that hip or knee osteoarthritis is associated with an elevated risk of frailty. These results remained robust and consistent across multiple calculation methods, including inverse variance weighted (OR = 1.082, 95% CI: 1.0532–1.1125, p = 1.36 × 10–8), MR‒Egger regression (OR = 1.175, 95% CI: 1.0162–1.3604, p = 0.040), weighted median estimation (OR = 1.078, 95% CI: 1.0365–1.1219, p = 1.831 × 10–4), weighted mode analysis (OR = 1.089, 95% CI: 1.0078–1.1771, p = 0.041) and simple mode analysis (OR = 1.093, 95% CI: 1.0112–1.1830, p = 0.034). Cochran’s Q test showed no evidence of heterogeneity among the IV estimates derived from individual variants, and the MR‒Egger regression analysis indicated that the presence of horizontal pleiotropy was unlikely to introduce bias into the results (intercept: –0.0044, p = 0.549). Conclusions Two-sample Mendelian randomization analysis effectively identified hip or knee osteoarthritis as a contributing risk factor for frailty.

Abstract Fixed frequency beam-scanning leaky-wave antennas have been a focus of attention for many scholars in recent years, and numerous related results have been obtained. However, these antennas suffer from several issues such as small beam-scanning range, low gain, and unsatisfactory impedance matching. To address these problems, this paper proposes a microstrip line (ML) antenna unit based on liquid crystal (LC) materials etched Complementary Split Ring Resonator (CSRR). In a first-of-its-kind approach, the substrate integrated waveguide (SIW) structure and the ML transmission structure are combined to present the SIW-ML transmission structure. The antenna operates in the Ka-band with excellent resonance characteristics at 34.7 GHz, and the S11 parameters are below − 13 dB in the frequency range of 30–40 GHz, indicating outstanding impedance matching. By arranging 56 antenna units, a periodic leaky-wave antenna is created, enabling fixed-frequency beam-scanning at 34.7 GHz. Experimental results show that the antenna can achieve scanning of angles between − 53° and + 60° with a gain of up to 12.63 dB. Once single-beam scanning is achieved, a method combining LC and discrete amplitude weighting technique, as well as multi-beam theory, is proposed for multi-beam study. Experimental results reveal that the designed 56-unit beam-scanning antenna can effectively realize beam scanning in two directions.

Abstract Serum uric acid (SUA) has been discovered to be associated with bone mineral density (BMD), but its relationship with trabecular bone score (TBS) remains unclear. Thus, the aim of our study was to investigate the association between SUA levels and TBS. Our study included 5895 individuals over 20 years old (3061 men and 2834 women) from NHANES 2005–2008. To analyze the association between SUA and TBS, multivariate linear regression models with covariate adjustments were applied. Furthermore, population description, stratified analysis, single factor analysis, smooth curve fitting, interaction analysis, and threshold effect and saturation effect analysis were also conducted. After adjusting for covariates, SUA showed a strong negative relationship with total TBS (β = 0.319; 95% CI 0.145–0.494; P

Abundant polyphenols make chokeberry have beneficial antioxidant and antiproliferative activity. In order to explore the contribution of different polyphenols in chokeberry to these activities, this study was conducted to determine polyphenol composition from 7 chokeberry varieties produced in China. Totally, 11 kinds of main polyphenol monomers were identified and quantified by UPLC-Q-TOF-MS and UPLC-PDA. HepG2 cells were used to evaluate their cellular antioxidant and antiproliferative activities. Partial least squares method was utilized to analyze multivariate correlations between proportion of different composition and monomers in total polyphenols with these activities. The results showed that the highest proportion in chokeberry polyphenols was proanthocyanidins. In comparing the bioactivities of 7 varieties of chokeberry, ‘Viking’ and purple chokeberry had the strongest antioxidant activity, while ‘Fukangyuan 1#’ had the strongest antiproliferative activity. In terms of the contribution sources of these bioactivities, the total antioxidant activity of chokeberry mainly depended on the contribution of free polyphenols. As the main source of cellular antioxidant activity, anthocyanins and neochlorogenic acid can provide more contribution. The antiproliferative activity mainly depended on the proportion of free polyphenols and proanthocyanidins in total polyphenols. The results may provide some new possibilities for the comprehensive utilization of polyphenols from chokeberry.

Scope: High-fat diet (HFD) induces imbalance in the small intestine environment, where fat digestion and absorption mainly take place. This study aimed to elucidate the mechanisms by which Lonicera caerulea polyphenols (LCP) might inhibit fat absorption, from the perspective of small intestine microbiota and epithelial barrier integrity. Methods and results: Male Sprague-Dawley rats were given HFD with or without co-administration of LCP for 8 weeks. The results showed that LCP supplementation significantly decreased the levels of serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), and increased the contents of fecal sterols, in HFD rats. LCP also inhibited the dysfunction of the small intestine epithelial barrier, via alleviating the oxidative stress activated by Nrf2-ARE pathway, and by modulating the expressions of pro-inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), nuclear factor kappa-B p65 (NF-κB p65) and inducible nitric oxide synthase (iNOS) in the small intestine. Additionally, LCP administration restored the balance in small intestine microbiota and increased the abundance of the specific bacteria, such as Lactobacillus, involved in fat absorption. Conclusion: Our results demonstrated that LCP may be beneficial to inhibit fat absorption. The mechanism seems to be associated with the protection of the epithelial barrier integrity and the modulation of specific bacteria in the small intestine.

Abstract Blueberry juice is one of deep‐processed products of blueberries, anthocyanins are main bioactive substance in blueberry juice. However, anthocyanins have poor stability. Thermal, high pressure, electric field, magnetic field and cobalt source irradiation were used to treat blueberry juice, and then the treated blueberry juice composition and antioxidant capacity were determined to explore ways to better protect anthocyanins. Metabolomics was used to qualitatively and quantitatively analyze the anthocyanins in blueberry juice, a total of 54 anthocyanins were identified. Different processing methods of treatment did not significantly change the types of anthocyanins in blueberry juice. Their effects were mainly focused on the changes in content. By determining the antioxidant capacity of blueberry juice, it was found that there is more than a simple linear relationship between the total anthocyanin content of blueberry juice and its antioxidant capacity. Therefore, the structural parameters of the four main anthocyanin monomers of blueberry juice were calculated using density functional theory to predict the antioxidant capacity and the antioxidant capacity of the monomers was determined for validation. The effect of different treatments on the change of antioxidant activity of blueberry juice due to anthocyanin occupancy was explained using equivalent antioxidant. The results showed that the 1 kGy irradiation treatment had a better protective effect on the anthocyanins, whereas the change in the percentage of anthocyanins due to this treatment was the key factor for the change in their antioxidant capacity.

Abstract Aronia melanocarpa is rich in anthocyanin, among which cyanidin‐3‐galactoside (C3G) is the most abundant. Here, we established an experimental model of mice and alveolar macrophage cell line MH‐S exposed to PM10, and C3G was administered to explore the underlying mechanism of C3G exerting protective effects on PM10‐induced lung inflammation. The results showed C3G alleviated PM10‐induced lung inflammation by reducing matrix metalloproteinases production at both gene and protein levels as well as pro‐inflammatory cytokine levels. Autophagy was activated in PM10‐injured alveolar macrophages (AMs), and C3G promoted autophagy indicated by LC3, BECN1, Atg5, Bcl‐2, and P62 expression, and C3G further resisted PM10‐induced AMs apoptosis. Besides, C3G could promote Pink1/Parkin‐mediated mitochondrial autophagy of AMs to alleviate the overexpression of mitochondrial reactive oxygen species (ROS) so that maintain mitochondrial membrane potential and ATP productions to restrict the distribution of Cyt‐c and further reduce the increasing of caspase 3/7 activity. Therefore, C3G enhanced the clearance of PM10‐damaged mitochondria by promoting AMs mitophagy, thereby reducing the activation of mitochondria‐dependent apoptosis pathway and the production of excess ROS, which reduced AMs apoptosis and secretion of pro‐inflammatory factors to ameliorate PM10‐induced pulmonary inflammation, suggesting that C3G may be as a functional food ingredient with the potential to improve lung health.

Abstract With the continuous improvement of people's living standards, food intake, bioactivity, and bioavailability have mainly concerned people. Therefore, the digestion and absorption of this kind of food have attracted people's attention. Some food has very high nutritional, medicinal, and medical value. However, because of its low conversion rate and utilization rate, the human body digests and absorbs less material, so the use of human value will be significantly reduced. Therefore, simulation and testing of digestion and absorption in vitro may be significant for dietary intake of bioactive substances. This paper reviews the organs and pathways of simulated food digestion and absorption in vitro and specific processing methods. In an in the vitro simulation system, the role of the human digestive system and absorption system in food digestion and absorption is described, and the performance of various simulation models, exceptionally dynamic in vitro models, is compared. Widespread use and refinement of these models will expand our understanding of the complex interplay of food substrates and digestive and absorptive systems. Therefore, it will be possible to design food with better bioavailability, more benefits to human health, and more targeted delivery, which is also in line with the development trend of food in the future.

This research aimed to study the preventive and relieving outcomes of kiwi berry on constipation. The administration of kiwi berries to mice resulted in a significant increase in body weight gain of 148.2% compared to mice that were constipated. The number of stools and the water content of stools both increased by 138.5% and 106.5%, respectively. The gastrointestinal transit rate increased by 45.3%, and the time it took for the first dark stool to form decreased by 57.5%. The levels of the excitability neurotransmitters were found to be higher in the group that had been given kiwi berries in comparison to the group that had been given loperamide. The opposite results were produced by vasoactive intestinal peptide (VIP) and aquaporin-3 (AQP3). In addition, kiwi berry consumption may lessen epithelial cell apoptosis and promote colon health. All the results point to kiwi berries as an extremely promising food supplement for the prevention and relief of constipation in the future since they successfully prevent and alleviate constipation brought on by loperamide.

Background: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. FBXO43, a member of the F‐box protein family, has been identified as a crucial prognostic factor in several cancers. However, its role in osteosarcoma remains largely unexplored. Methods: This study investigated the expression and potential role of FBXO43 across the TCGA pan‐cancer cohort, with a particular focus on sarcoma (SARC). We analyzed the relationship between FBXO43 expression and various cancer‐related pathways, immune infiltration, and genomic features, including TP53 mutations. We also conducted immunotherapy predictive analyses using TIDE and Submap algorithms. To validate our findings, we performed a series of in vitro experiments, including cell invasion and wound healing assays. Results: FBXO43 was found to be significantly overexpressed in various cancers and was particularly associated with pathways such as E2F_TARGETS and G2M_CHECKPOINT in SARC samples. Differential FBXO43 expression was linked to distinct immune infiltration patterns and pathway enrichments. Notably, high FBXO43 expression in osteosarcoma was associated with a higher TP53 mutation rate. Predictive analyses indicated that patients with low FBXO43 expression had better immunotherapy responses, suggesting its potential as a diagnostic and prognostic biomarker. These findings were corroborated by our in vitro functional assays. Conclusion: Our comprehensive analysis reveals that FBXO43 plays a critical role in the progression of osteosarcoma, impacting both immune infiltration and genomic stability. FBXO43 expression levels may serve as valuable biomarkers for predicting immunotherapy responses in osteosarcoma patients. Future studies should aim to elucidate the molecular mechanisms driving FBXO43's role and validating these findings in clinical settings to develop targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

Abstract Background The overall response rate to checkpoint blockade remains unsatisfactory, partially due to the immune-suppressive tumor microenvironment. A retinoic acid-related orphan receptor γt (RORγt) agonist (LYC-55716) is currently used in clinical trials combined with anti-PD-1, but how the Th17 cell transcription factor RORγt enhances antitumor immunity of PD-1 in the tumor microenvironment remains elusive. Methods The expression of mRNA was analyzed using qPCR assays. Flow cytometry was used to sort and profile cells. Cell migration was analyzed using Transwell assays. Biacore was used to determine the binding affinity to the RORγt protein. The RORγt GAL4 cell-based reporter gene assay was used to measure activity in the RORγt driven luciferase reporter gene expression. Results We designed a potent and selective small-molecule RORγt agonist (8-074) that shows robust antitumor efficacy in syngeneic tumor models and improves the efficacy of anti‑PD‑1 in a murine lung cancer model. RORγt agonist treatment increased intratumoral CD8+ T cells, which were correlated with CXCL10 and monocyte-derived dendritic cells (MoDCs). In addition, the RORγt agonist promoted Type 17 T cell migration by upregulating CCL20 and CCR6 expression, and Type 17 T cell tumor infiltration. CCL20 induces MoDCs migration, and CXCL10 derived from MoDCs promotes CD8+ T cell migration. Conclusion Our results revealed that the RORγt agonist improved the efficacy of anti-PD-1. The RORγt agonist increased the migration of MoDCs, which increased the local levels of CXCL10, thus promoting CD8+ T cell tumor infiltration. Our findings provide the mechanistic insights implicating the RORγt agonist in immunotherapy and offer a strategy for targeting the RORγt agonist to improve PD-1 antibody efficacy in cancers.

The prevalence of type 2 diabetes mellitus (T2DM) is increasing every year. Medications are currently the most common therapy for T2DM. However, these medications have certain adverse effects. In order to find safe and effective ways to improve this disease, researchers have discovered that some natural products can decrease blood sugar. Flavonoids are one of the most essential low molecular weight phenolic chemicals in the plant world, which widely exist in plant roots, stems, leaves, flowers, and fruits. They possess a variety of biological activities, including organ protection, hypoglycemic, lipid-lowering, anti-oxidative and anti-inflammatory effects. Some natural flavonoids ameliorate T2DM and its complications through anti-oxidation, anti-inflammatory action, glucose and lipid metabolism regulation, insulin resistance management, etc. Hence, this review aims at demonstrating the potential benefits of flavonoids in T2DM and its complications. This laid the foundation for the development of novel hypoglycemic medications from flavonoids.

BackgroundBone metastasis is a common adverse event in kidney cancer, often resulting in poor survival. However, tools for predicting KCBM and assessing survival after KCBM have not performed well.MethodsThe study uses machine learning to build models for assessing kidney cancer bone metastasis risk, prognosis, and performance evaluation. We selected 71,414 kidney cancer patients from SEER database between 2010 and 2016. Additionally, 963 patients with kidney cancer from an independent medical center were chosen to validate the performance. In the next step, eight different machine learning methods were applied to develop KCBM diagnosis and prognosis models while the risk factors were identified from univariate and multivariate logistic regression and the prognosis factors were analyzed through Kaplan-Meier survival curve and Cox proportional hazards regression. The performance of the models was compared with current models, including the logistic regression model and the AJCC TNM staging model, applying receiver operating characteristics, decision curve analysis, and the calculation of accuracy and sensitivity in both internal and independent external cohorts.ResultsOur prognosis model achieved an AUC of 0.8269 (95%CI: 0.8083–0.8425) in the internal validation cohort and 0.9123 (95%CI: 0.8979–0.9261) in the external validation cohort. In addition, we tested the performance of the extreme gradient boosting model through decision curve analysis curve, Precision-Recall curve, and Brier score and two models exhibited excellent performance.ConclusionOur developed models can accurately predict the risk and prognosis of KCBM and contribute to helping improve decision-making.

With the continuous growth of global energy demand and the late stage of conventional oilfield exploitation, the demand for developing and utilizing low-permeability heavy oil reservoirs is becoming increasingly urgent. However, the exploitation of low-permeability heavy oil reservoirs faces many challenges due to their high viscosity, low permeability, and complex geological conditions. To overcome these challenges, researchers have gradually introduced SC-CO2 as an oil displacement agent in the exploitation of heavy oil reservoirs. However, the oil displacement mechanism of SC-CO2 in low-permeability heavy oil reservoirs and its improvement mechanism are still not completely understood. The article provides a detailed study and understanding of the oil displacement mechanism of SC-CO2, which involves the expansion of heavy oil volume through SC-CO2 dissolution. This mechanism reduces the capillary resistance and flow resistance during the oil flow process. The permeation of CO2 disrupts the internal structure and arrangement of heavy oil, reducing its viscosity. CO2 extracts both light and heavy components from the heavy oil, reducing the residual oil saturation. In addition, the mechanism of improving the effect of oil displacement agents such as nanoparticles, polymers, and surfactants on SC-CO2 displacement was also explored. By further exploring the mechanisms and improvement mechanisms of SC-CO2 displacement for heavy oil, it can guide the selection and optimization of oil displacement agents. Furthermore, understanding the mechanism can also provide a theoretical basis for engineering practice and technical innovation. While the research on CO2 flooding is analyzed and evaluated, the obstacles and challenges that still exist at this stage are indicated, and future research work on CO2 in low-permeability heavy oil reservoirs is proposed.

Malvidin-3-galactoside (Mv-3-gal) is the major anthocyanin monomer in blueberry anthocyanins. The compound is well-characterized by its anti-oncogenesis function in multiple organs including liver. In the current study, the mechanism driving the anti-hepatocellular carcinoma (HCC) function of Mv-3-gal was further explored by focusing on apoptosis and metastases pathways. HCC cell line Huh-7 was firstly administrated with Mv-3-gal of different concentrations and the effect of Mv-3-gal on cell proliferation, apoptosis, colony formation ability, metastasis potential as well as the activity of Akt/PTEN and MAPK pathways was assessed. The results showed that Mv-3-gal inhibited the cell proliferation and colony formation ability, induced cell cycle arrest and apoptosis in a dose-dependent manner. Regarding the metastasis potential, Mv-3-gal suppressed the migration and invasion potential of Huh-7 cells by regulating MMPs expression. Taken together, the findings highlighted the anti-HCC potent of Mv-3-gal, which was associated with the inhibition of Akt/PTEN, MAPK and MMP pathways.

Aflatoxin B1 (AFB1) causes oxidative stress and hepatocyte apoptosis through its epoxidized metabolite AFBO, which is catalyzed by CYP450 enzymes. Ferulic acid (FA) is a phenolic acid commonly found in plants and is known for its antioxidant capacity. However, the role of FA in AFB1-induced liver injury is still elusive. In this study, rats were exposed to AFB1 and simultaneously treated with FA for 30 days. The results showed that I) FA alleviated the histopathological changes induced by AFB1, inhibited the elevation of serological indexes induced by AFB1, and reduced the production of AFBO in liver. II) AFB1-induced increase in CYP450 expression was significantly reduced by FA. The molecular docking results of FA and CYP2A6 showed high fitness score and interaction. III) FA obviously inhibited the production of MDA, and significantly activated the Nrf2/GST pathway and antioxidant enzymes (SOD and GST). IV) AFB1-induced hepatocyte apoptosis, the high expression of p53, bax, cyt-c, caspase-9, caspase-3, and the low expression of bcl-2 were all restored by FA. It has been suggested from these results that FA proved effective against AFB1-induced liver damage in rats via inhibiting CYP450 enzyme, promoting antioxidant pathway Nrf2/GST, activating antioxidant enzymes (SOD and GST), and regulating the mitochondrial pathway.

In view of the problem that the Density Peaks Clustering (DPC) algorithm needs to manually set the parameter cut-off distance (dc) we propose a Wolf Pack optimization theory based Density Peaks Clustering approach (WPA-DPC). Firstly, we introduce dc parameter into the Wolf Pack Algorithm (WPA) to speed up the search. Secondly, we introduce the WPA into the DPC algorithm; the cut-off distance is used as the location of the wolf group. Finally, we make silhouette index in the search process as the fitness value, and the optimal location of the wolf group is the parameter value at the end. The simulation results show that compared with the traditional Density Peaks Clustering algorithm, the proposed algorithm is closer to the true clustering number. According to the evaluation results of silhouette and f-measure, the quality of clustering and the accuracy are greatly improved.

The kiwi berry (Actinidia arguta) has been widely studied because of its rich phenolic, flavonoid, and vitamin C contents. Numerous reports have demonstrated that fruit peels contain higher phenolic content and antioxidant activity than that of flesh. In this study, the phytochemical content and antioxidant activities of peel and flesh extracts of six kiwi berries were analyzed from four regions (namely, Dandong, Benxi, Taian, and Tonghua) in China. The antioxidant activity was determined using the peroxyl radical scavenging capacity (PSC) and cellular antioxidant activity (CAA) assays. The phenolic, flavonoid, and vitamin C contents of kiwi berry peel were 10.77, 13.09, and 10.38 times richer than that of kiwi berry flesh, respectively. In addition, the PSC and CAA values of kiwi berry peel were higher than those of kiwi berry flesh. The analysis of the separation and contents of phenolics were performed by the high-performance liquid chromatography (HPLC)-diode-array detectormass spectrometry/mass (DAD-MS/MS) system, and the results illustrated that protocatechuic acid, caffeic acid, chlorogenic acid, and quinic acid were the major phenolic compounds. In conclusion, this study indicated that kiwi berry peel contains a rich source of antioxidants. These data are of great significance for the full development and utilization of kiwi berries in these four regions of China to produce nutraceutical and functional foods.

Helicobacter pylori (HP) contributes to the development of gastrointestinal disorders. Cyanidin-3-O-glucoside (C3G) is a major anthocyanin in human diets. In the current study, the effects and associated mechanism of C3G on HP lipopolysaccharide (LPS)-induced symptoms on human gastric epithelial cell (HGEC) cells were explored. The cells were exposed to LPS and C3G, and cellular viability, apoptotic rate, inflammation level, and toll-like receptor (TLR)-mediated nuclear factor-kappa B (NF-κB) pathway activity were measured. C3G suppressed the abnormal DNA synthesis and induced apoptosis in LPS-treated HGEC cells. C3G also reduced inflammation in LPS-treated HGEC cells. Although C3G exposure reduced the expressions of TLR2 and TLR4, it had no influence on TLR5. C3G deactivated TLR-mediated NF-κB signaling. The effects of C3G were stronger than anthocyanin extract but weaker than curcumin. The protective effects of C3G against HP LPS-induced injuries in gastric epithelial cells were associated with the deactivation of TLR2- and TLR4-mediated NF-κB signaling.

Cyanidin-3-glucoside (C3G) is an abundant anthocyanin that exhibits antimicrobial, cardioprotective, and hepatoprotective effects. We applied C3G to silica-injured mice to investigate the efficacy of dietary C3G on lung inflammation and the underlying action mechanism as this information is currently unavailable. We found that C3G treatment significantly alleviated lung inflammation and reduced inflammatory cell infiltration into the lungs. It also reduced the pro-inflammatory cytokine levels in bronchoalveolar lavage fluid. Flow cytometry analysis revealed that C3G treatment ameliorated pulmonary helper and cytotoxic T cell immune responses by decreasing cytokine levels. Regulatory T cells and IL-17A producing-regulatory T cells were also decreased by C3G treatment. Furthermore, C3G effectively suppressed SP-induced activation of the STAT1 and STAT3 signaling pathways of lung tissues. These results demonstrated that dietary C3G could alleviate SP induced lung injury in mice and support the use of C3G as functional food to modulate pulmonary immune responses to silica particles.

A mangiferin aglycon derivative J99745 has been identified as a potent xanthine oxidase (XOD) inhibitor by previous in vitro study. This study aimed to evaluate the hypouricemic effects of J99745 in experimental hyperuricemia mice, and explore the underlying mechanisms. Mice were orally administered 600 mg/kg xanthine once daily for 7 days and intraperitoneally injected 250 mg/kg oxonic acid on the 7th day to induce hyperuricemia. Meanwhile, J99745 (3, 10, and 30 mg/kg), allopurinol (20 mg/kg) or benzbromarone (20 mg/kg) were orally administered to mice for 7 days. On the 7th day, uric acid and creatinine in serum and urine, blood urea nitrogen (BUN), malondialdehyde (MDA) content and XOD activities in serum and liver were determined. Morphological changes in kidney were observed using hematoxylin and eosin (H&E) staining. Hepatic XOD, renal urate transporter 1 (URAT1), glucose transporter type 9 (GLUT9), organic anion transporter 1 (OAT1) and ATP-binding cassette transporter G2 (ABCG2) were detected by Western blot and real time polymerase chain reaction (PCR). The results showed that J99745 at doses of 10 and 30 mg/kg significantly reduced serum urate, and enhanced fractional excretion of uric acid (FEUA). H&E staining confirmed that J99745 provided greater nephroprotective effects than allopurinol and benzbromarone. Moreover, serum and hepatic XOD activities and renal URAT1 expression declined in J99745-treated hyperuricemia mice. In consistence with the ability to inhibit XOD, J99745 lowered serum MDA content in hyperuricemia mice. Our results suggest that J99745 exerts urate-lowering effect by inhibiting XOD activity and URAT1 expression, thus representing a promising candidate as an anti-hyperuricemia agent. KEY WORDS: Antihyperuricemic effect, Mangiferin aglycon, Derivative, Xanthine oxidase, Urate transporter 1