Preparation and epitope analysis of monoclonal antibodies against African swine fever virus DP96R protein.

BACKGROUND: Many proteins of African swine fever virus (ASFV, such as p72, p54, p30, CD2v, K205R) have been successfully expressed and characterized. However, there are few reports on the DP96R protein of ASFV, which is the virulence protein of ASFV and plays an important role in the process of host infection and invasion of ASFV. RESULTS: Firstly, the prokaryotic expression vector of DP96R gene was constructed, the prokaryotic system was used to induce the expression of DP96R protein, and monoclonal antibody was prepared by immunizing mice. Four monoclonal cells of DP96R protein were obtained by three ELISA screening and two sub-cloning; the titer of ascites antibody was up to 1:500,000, and the monoclonal antibody could specifically recognize DP96R protein. Finally, the subtypes of the four strains of monoclonal antibodies were identified and the minimum epitopes recognized by them were determined. CONCLUSION: Monoclonal antibody against ASFV DP96R protein was successfully prepared and identified, which lays a foundation for further exploration of the structure and function of DP96R protein and ASFV diagnostic technology.

Identification of a fatty acid metabolism-related gene signature to predict prognosis in stomach adenocarcinoma.

BACKGROUND: Fatty acid metabolism (FAM) contributes to tumorigenesis and tumor development, but the role of FAM in the progression of stomach adenocarcinoma (STAD) has not been comprehensively clarified. METHODS: The expression data and clinical follow-up information were obtained from The Cancer Genome Atlas (TCGA). FAM pathway was analyzed by gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) methods. Univariate Cox regression analysis was conducted to select prognosis genes. Molecular subtypes were classified by consensus clustering analysis. Furthermore, least absolute shrinkage and selection operator (Lasso) analysis was employed to develop a risk model. ESTIMATE and tumour immune dysfunction and exclusion (TIDE) algorithm were used to assess immunity. pRRophetic package was conducted to predict drug sensitivity. RESULTS: Based on 14 FAM related prognosis genes (FAMRG), 2 clusters were determined. Patients in C2 showed a worse overall survival (OS). Furthermore, a 7-FAMRG risk model was established as an independent predictor for STAD, with a higher riskscore indicating an unfavorable OS. High riskscore patients had higher TIDE score and these patients were more sensitive to anticancer drugs such as Bortezomib, Dasatinib and Pazopanib. A nomogram based on riskscore was an effective prediction tool applicable to clinical settings. The results from pan-cancer analysis supported a prominent application value of riskscore model in other cancer types. CONCLUSION: The FAMRGs model established in this study could help predict STAD prognosis and offer new directions for future studies on dysfunctional FAM-induced damage and anti-tumor drugs in STAD disease.

Long non-coding RNA-NONMMMUT004552.2 regulates the unloading-induced bone loss through the miRNA-15b-5p/Syne1 in mice.

Exercise-induced mechanical loading can increase bone strength whilst mechanical unloading enhances bone-loss. Here, we investigated the role of lncRNA NONMMUT004552.2 in unloading-induced bone-loss. Knockout of lncRNA NONMMUT004552.2 in hindlimb-unloaded mice caused an increase in the bone formation and osteoblast activity. The silencing of lncRNA NONMMUT004552.2 also decreased the osteoblast apoptosis and expression of Bax and cleaved caspase-3, increased Bcl-2 protein expression in MC3T3-E1 cells. Mechanistic investigations demonstrated that NONMMUT004552.2 functions as a competing endogenous RNA (ceRNA) to facilitate the protein expression of spectrin repeat containing, nuclear envelope 1 (Syne1) by competitively binding miR-15b-5p and subsequently inhibits the osteoblast differentiation and bone formation in the microgravity unloading environment. These data highlight the importance of the lncRNA NONMMUT004552.2/miR-15b-5p/Syne1 axis for the treatment of osteoporosis.

Signature of Sr isotope ratios and the contents of elements as a tool to distinguish wine regions in China.

This study investigated 120 Chinese wines from seven regions and had two objectives: to clarify the Sr isotope ratios and elemental characteristics of each region and to develop a strategy to distinguish the geographic origin of wine without authentic samples to predict its origin. The analyzed 87Sr/86Sr values ranged from 0.708256 to 0.715148, which correlated with the geological characteristics of the regions where they were grown. The Hexi Corridor exhibited the highest ratios of Sr isotopes, while Xinjiang had the lowest. The 87Sr/86Sr values were applied to establish a prediction map which was evaluated through cross-validation. The prediction error was found to be less than 0.00074. The Sr isotope ratio could remain stable for an extended period in a specific location. This map shows the feasibility of identifying wine origin and could be applied to other food products. Adding Sr isotope ratios could improve the accuracy in tracing wine origin.

Effects of Semen Ziziphi Spinosae extract and binary probiotics co-fermentation on the quality of yogurt and their underlying molecular mechanisms.

The study aimed to investigate the impact of water-soluble extract from Semen Ziziphi Spinosae (SZSE) on yogurt quality and understand the underlying mechanism. The results demonstrated that adding 0.5% (w/v) SZSE had a significant effect on reducing yogurt syneresis and resulted in a more compact and uniform casein gel. Notably, the co-fermented yogurt with binary probiotics (Lacticaseibacillus casei CGMCC1.5956 and Levilactobacillus brevis CGMCC1.5954) along with SZSE led to increased viable probiotics and a higher odor score (23.23). This effect might be attributed to the increased amino acid utilization by binary probiotics through biosynthesis of valine, leucine and isoleucine, metabolic pathways, and amino acid biosynthesis to produce amino acid derivatives such as N5-(l-1-carboxyethyl)-l-ornithine and diaminopyrimidine acid. The yogurt contained 79 volatile flavor compounds, with hexanoic acid, 2-heptanone, and 2-nonanone potentially contributing to the high odor scores. These findings have strategic implications for developing yogurt with high gel characteristics and distinctive flavor.

Effect of Forced Convection on Magnesium Dendrite: Comparison between Constant and Altering Flow Fields.

Convection has a nonnegligible effect on the growth of the magnesium dendrite with six-primary-branch pattern. Most work, however, investigates the effect of the convection by simplifying the melt flow as a constant horizontal flow. In this work, four convection behaviors, including equally distributed convection, linearly distributed convection, sinusoidal-wave convection, and square-wave convection, are imposed and simulated through the phase-field lattice-Boltzmann schemes. The effects of constant (the former two) and altering (the latter two) flow fields are quantified by the length ratio of the upstream primary arm to the downstream one. The results show that the dendrite asymmetry increases under the constant forced convections but presents nonmonotonic change under the altering convections. A simple mathematical relation is fitted to summarize the dependence of the dendrite asymmetry on the input velocity, the undercooling, and the flow frequency. Deep understanding of the convection effects can guide the prediction and control of the magnesium dendrite under more complex situations.

The impact of main Areca Catechu root exudates on soil microbial community structure and function in coffee plantation soils.

Coffee is an important cash crop worldwide, but it has been plagued by serious continuous planting obstacles. Intercropping with Areca catechu could alleviate the continuous planting obstacle of coffee due to the diverse root secretions of Areca catechu. However, the mechanism of Areca catechu root secretion in alleviating coffee continuous planting obstacle is still unclear. The changes of coffee rhizosphere soil microbial compositions and functions were explored by adding simulated root secretions of Areca catechu, the primary intercropping plant species (i.e., amino acids, plant hormone, organic acids, phenolic acids, flavonoids and sugars) in current study. The results showed that the addition of coffee root exudates altered soil physicochemical properties, with significantly increasing the availability of potassium and organic matter contents as well as promoting soil enzyme activity. However, the addition of plant hormone, organic acids, or phenolic acids led to a decrease in the Shannon index of bacterial communities in continuously planted coffee rhizosphere soil (RS-CP). The inclusion of phenolic acids specifically caused the decrease of fungal Shannon index. Plant hormone, flavonoids, phenolic acids, and sugars increased the relative abundance of beneficial bacteria with reduced bacterial pathogens. Flavonoids and organic acids increased the relative abundance of potential fungal pathogen Fusarium. The polyphenol oxidase, dehydrogenase, urease, catalase, and pH were highly linked with bacterial community structure. Moreover, catalase, pH, and soil-available potassium were the main determinants of fungal communities. In conclusion, this study highlight that the addition of plant hormone, phenolic acids, and sugars could enhance enzyme activity, and promote synergistic interactions among microorganisms by enhancing the physicochemical properties of RS-CP, maintaining the soil functions in coffee continuous planting soil, which contribute to alleviate the obstacles associated with continuous coffee cultivation.

Reduced nitrogen fertilization from pre-flowering to pre-veraison alters phenolic profiles of Vitis vinifera L. Cv. Cabernet Gernischt wine of Yantai, China.

Nitrogen (N) fertilization is important for grape growth and wine quality. Unreasonable N fertilizer application affects wine growth and has a negative impact on wine quality. Therefore, it is essential to address the mismatch between N application and wine composition. To regulate vine growth and improve grape and wine quality, Cabernet Gernischt (Vitis vinifera L.) grapevines were subjected to lower levels of N, compared to normal N supply treatments, during the grape growing seasons of 2019 and 2020 in the wine region of Yantai, China. The effects of reduced N application from pre-boom to pre-veraison on vine growth, yield and composition of grapes, and dry red wine anthocyanin and non-anthocyanin phenolic compound content were studied. We found that reduced N application significantly decreased dormant shoot fresh mass and yield. However, the effect of N application on fruit ripening depended on the season. Nitrogen-reduction treatment significantly improved wine phenolic parameters, including total phenolics, tannins, and anthocyanins, and enhanced most of the individual anthocyanins and some non-anthocyanin phenolics, especially stilbenes, including piceatannol, trans-resveratrol, and polydatin, regardless of the season. Overall, our findings highlight the importance of reducing N application during the grape growing season in order to modify the wine phenolic profiles.

Targeting and cytotoxicity of chimeric antigen receptor T cells grafted with PD1 extramembrane domain.

BACKGROUND: Immunosuppression induced by programmed cell death protein 1 (PD1) presents a significant constraint on the effectiveness of chimeric antigen receptor (CAR)-T therapy. The potential of combining PD1/PDL1 (Programmed cell death 1 ligand 1) axis blockade with CAR-T cell therapy is promising. However, developing a highly efficient and minimally toxic approach requires further exploration. Our attempt to devise a novel CAR structure capable of recognizing both tumor antigens and PDL1 encountered challenges since direct targeting of PDL1 resulted in systemic adverse effects. METHODS: In this research, we innovatively engineered novel CARs by grafting the PD1 domain into a conventional second-generation (2G) CAR specifically targeting CD19. These CARs exist in two distinct forms: one with PD1 extramembrane domain (EMD) directly linked to a transmembrane domain (TMD), referred to as PE CAR, and the other with PD1 EMD connected to a TMD via a CD8 hinge domain (HD), known as PE8HT CAR. To evaluate their efficacy, we conducted comprehensive assessments of their cytotoxicity, cytokine release, and potential off-target effects both in vitro and in vivo using tumor models that overexpress CD19/PDL1. RESULTS: The findings of our study indicate that PE CAR demonstrates enhanced cytotoxicity and reduced cytokine release specifically towards CD19 + PDL1 + tumor cells, without off-target effects to CD19-PDL1 + tumor cells, in contrast to 2G CAR-T cells. Additionally, PE CAR showed ameliorative differentiation, exhaustion, and apoptosis phenotypes as assessed by flow cytometry, RNA-sequencing, and metabolic parameter analysis, after encountering CD19 + PDL1 + tumor cells. CONCLUSION: Our results revealed that CAR grafted with PD1 exhibits enhanced antitumor activity with lower cytokine release and no PD1-related off-target toxicity in tumor models that overexpress CD19 and PDL1. These findings suggest that our CAR design holds the potential for effectively addressing the PD1 signal.

Differentiation in TCM patterns of chronic obstructive pulmonary disease by comprehensive metabolomic and lipidomic characterization.

Introduction: Chronic obstructive pulmonary disease (COPD) is a complex disease involving inflammation, cell senescence, and autoimmunity. Dialectical treatment for COPD with traditional Chinese medicine (TCM) has the advantage of fewer side effects, more effective suppression of inflammation, and improved immune function. However, the biological base of TCM pattern differentiation in COPD remains unclear. Methods: Liquid Chromatography-Quadrupole-Orbitrap mass spectrometry (LC-Q-Orbitrap MS/MS) based metabolomics and lipidomics were used to analyze the serum samples from COPD patients of three TCM patterns in Lung Qi Deficiency (n=65), Lung-Kidney Qi Deficiency (n=54), Lung-Spleen Qi Deficiency (n=52), and healthy subjects (n=41). Three cross-comparisons were performed to characterize metabolic markers for different TCM patterns of COPD vs healthy subjects. Results: We identified 28, 8, and 16 metabolites with differential abundance between three TCM patterns of COPD vs healthy subjects, respectively, the metabolic markers included cortisol, hypoxanthine, fatty acids, alkyl-/alkenyl-substituted phosphatidylethanolamine, and phosphatidylcholine, etc. Three panels of metabolic biomarkers specific to the above three TCM patterns yielded areas under the receiver operating characteristic curve of 0.992, 0.881, and 0.928, respectively, with sensitivity of 97.1%, 88.6%, and 91.4%, respectively, and specificity of 96.4%, 81.8%, and 83.9%, respectively. Discussion: Combining metabolomics and lipidomics can more comprehensively and accurately trace metabolic markers. As a result, the differences in metabolism were proven to underlie different TCM patterns of COPD, which provided evidence to aid our understanding of the biological basis of dialectical treatment, and can also serve as biomarkers for more accurate diagnosis.

Conjugated Polymeric Materials in Biological Imaging and Cancer Therapy.

Conjugated polymers (CPs) have attracted much attention in the fields of chemistry, medicine, life science, and material science. Researchers have carried out a series of innovative researches and have made significant research progress regarding the unique photochemical and photophysical properties of CPs, expanding the application range of polymers. CPs are polymers formed by the conjugation of multiple repeating light-emitting units. Through precise control of their structure, functional molecules with different properties can be obtained. Fluorescence probes with different absorption and emission wavelengths can be obtained by changing the main chain structure. By modifying the side chain structure with water-soluble groups or selective recognition molecules, electrostatic interaction or specific binding with specific targets can be achieved; subsequently, the purpose of selective recognition can be achieved. This article reviews the research work of CPs in cell imaging, tumor diagnosis, and treatment in recent years, summarizes the latest progress in the application of CPs in imaging, tumor diagnosis, and treatment, and discusses the future development direction of CPs in cell imaging, tumor diagnosis, and treatment.

Effects of Hevea brasiliensis Intercropping on the Volatiles of Pandanus amaryllifolius Leaves.

Pandanus amaryllifolius Roxb. is a special tropical spice crop resource with broad development prospects. It is widely cultivated under a Hevea brasiliensis (Willd. ex A. Juss.) Muell. Arg. canopy to improve the comprehensive benefits to Hevea brasiliensis plantations in Hainan Provence, China. However, the effects of intercropping with Hevea brasiliensis on the component number and relative contents of volatile substances in different categories in the Pandanus amaryllifolius leaves are still unknown. Therefore, a Hevea brasiliensis and Pandanus amaryllifolius intercropping experiment was set up to clarify the differences between several cultivated patterns on volatile substances in the Pandanus amaryllifolius leaves, and the key regulatory factors of volatile substances. The results showed that the soil pH was significantly decreased, while soil bulk density, alkali-hydrolyzable nitrogen and available phosphorus contents were significantly increased under the intercropping pattern. The component numbers of esters in volatile substances were increased by 6.20%, while the component numbers of ketones were decreased by 4.26% under the intercropping pattern. Compared with the Pandanus amaryllifolius monoculture, the relative contents of pyrroles, esters and furanones were significantly increased by 8.83%, 2.30% and 8.27%, respectively, while the relative contents of ketones, furans and hydrocarbons were decreased by 1.01%, 10.55% and 9.16% under the intercropping pattern, respectively. The relative contents of pyrroles, esters, furanones, ketones, furans and hydrocarbons were associated with changes in soil pH, soil available phosphorus content and air temperature. The results indicated that the reduction in soil pH and enhancement in soil-available phosphorus may be the main reasons for promoting the relative content of pyrroles and reducing the relative content of hydrocarbons under an intercropping pattern. Overall, Hevea brasiliensis intercropping with Pandanus amaryllifolius could not only improve soil properties, but also significantly increase the relative contents of the main volatile substances in Pandanus amaryllifolius leaves, which could provide a theoretical basis for the application and promotion of high-quality production patterns of Pandanus amaryllifolius.

Modification of wine phenolic profiles by gibberellic acid application in 'Cabernet Gernischt' grapevines before anthesis.

BACKGROUND: Vitis vinifera L. 'Cabernet Gernischt' grapes from the Yantai wine region of China usually form dense clusters and contain low phenolic content. We applied five concentrations (ranged from 5 to 25 mg L-1 ) of gibberellic acid (GA3 ) to 'Cabernet Gernischt' before anthesis to decrease cluster compactness in two consecutive vintages. Yield indices, grape maturity, and wine phenolic compounds were determined. RESULTS: GA3 application significantly reduced cluster compactness, bunch weight, and yield per vine, but it did not significantly improve fruit ripening. The levels of total phenolics, total tannins, and total anthocyanins in wine were enhanced by GA3 application, with 10 and 15 mg L-1 GA3 treatments consistently producing a significant increase in the concentrations of mavidin, cyanidin, and their derivatives. Specifically, trans-resveratrol was consistently significantly increased by 15 mg L-1 GA3 application. Principal component analysis of phenolic compounds demonstrated the differences among wines produced from GA3 treatment groups and the control. CONCLUSION: Overall, wine phenolic profiles could be significantly modified by application of low concentrations of GA3 before anthesis. Application of high levels of GA3 is not recommended due to significant yield decrease. © 2022 Society of Chemical Industry.

Effects of coffee pericarp and litter mulsching on soil microbiomes diversity and functions in a tropical coffee plantation, South China.

In recent decades, ecological cyclic cultivation models have attracted increasing attention, primarily because the decomposition of crop residues and litter enhances soil organic matter content, thereby altering the soil microenvironment and regulating the diversity and functions of soil microbial communities. However, the effects of different coffee waste mulching on the diversity of soil microbial communities and their functions are still unclear. Therefore, this study set up four kinds of covering treatments: uncovered coffee waste (C), covered coffee litter (L), covered coffee pericarp (P), and both covered coffee litter and pericarp (PL). The results showed that compared to the control, coffee pericarp mulching significantly increased the soil available potassium (SAK) content by 18.45% and alkali hydrolyzed N (SAN) content by 17.29%. Furthermore, coffee pericarp mulching significantly increased bacterial richness and diversity by 7.75 and 2.79%, respectively, while litter mulching had little effect on bacterial abundance and diversity was smaller. The pericarp mulching significantly increased the abundance of Proteus by 22.35% and the abundance of Chlamydomonas by 80.04%, but significantly decreased the abundance of Cyanobacteria by 68.38%, while the coffee litter mulching significantly increased the abundance of Chlamydomonas by 48.28%, but significantly decreased the abundance of Cyanobacteria by 73.98%. The increase in soil SAK promoted bacterial Anoxygenic_photoautotrophy, Nitrogen_respiration, Nitrate_respiration, Nitrite_respiration, and Denitrification functions. The above results indicate that the increase in available soil potassium and alkali hydrolyzed N content under coffee pericarp cover is the main reason for promoting the diversity and richness of bacterial community and promoting the changes in bacterial community structure and function. The use of coffee pericarps in coffee plantations for ecological recycling helps to improve the diversity of the soil microbial community and maintain the relative stability of the microbial community structure and function, promoting soil health conservation and the sustainable development of related industries.

Preparation and Characterization of In Situ (TiC-TiB2)/Al-Cu-Mg-Si Composites with High Strength and Wear Resistance.

This study involved the preparation and characterization of in situ (TiC-TiB2)/Al-4.7Cu-0.32Mg-0.44Si composites with excellent mechanical and abrasive wear properties. The composites were synthesized in an Al-Ti-B4C system by combining combustion reaction synthesis with hot-pressed sintering and hot extrusion. The in situ TiB2 and TiC particles were of multi-scaled sizes ranging from 20 nm to 1.3 µm. The TiB2 and TiC particles effectively increased the yield strength (σ0.2), ultimate tensile strength (σUTS), hardness (HV), and abrasive wear resistance of the composites. The 40 wt.% (TiC-TiB2)/Al-4.7Cu-0.32Mg-0.44Si composite exhibited the highest σ0.2 (569 MPa), σUTS (704 MPa) and hardness (286 HV), which were 74%, 51% and 110% higher than those of the matrix alloy, respectively. Compared with the matrix alloy, the abrasive wear resistance of the 40 wt.% (TiC-TiB2)/Al-4.7Cu-0.32Mg-0.44Si composite was increased by 4.17 times under an applied load of 5 N and Al2O3 abrasive particle size of 13 µm. Micro-ploughing and micro-cutting were the main abrasive wear mechanisms for the Al-Cu-Mg-Si alloy and the composites.

Chemical Identification and Antioxidant Screening of Bufei Yishen Formula using an Offline DPPH Ultrahigh-Performance Liquid Chromatography Q-Extractive Orbitrap MS/MS.

Chronic obstructive pulmonary disease (COPD) has high morbidity and mortality and presents a threat to human health worldwide. Numerous clinical trials have confirmed that Bufei Yishen formula (BYF), an herbal medicine, can alleviate the symptoms of COPD by reducing oxidative stress-mediated inflammation. However, the active components of BYF remain unclear. We developed an efficient ultrahigh-performance liquid chromatography Q-Extractive Orbitrap mass spectrometry method to identify the composition of BYF and determine its antioxidant profile through an offline screening strategy based on 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH)-liquid chromatography-mass spectrometry. In total, 189 compounds were identified in BYF extract, including 83 flavonoids, 24 lignans, 20 alkaloids, 15 saponins, 11 terpenoid, 10 saccharides, eight lipids, seven organic acids, two coumarins, two amino acids, and seven other compounds. Among them, 79 compounds were found to have a potential antioxidant activity. In vitro validation indicated that the free radical scavenging activities of rosmarinic acid and calycosin were similar to that of the positive control (DPPH IC50 = 25.72 ± 1.02 and 147.23 ± 25.12 µg/mL, respectively). Furthermore, calycosin had a high content in serum after the oral administration of BYF, indicating that calycosin might be the major antioxidant compound in BYF.

Co-winemaking with Vitis amurensis Rupr. "Beibinghong" enhances the quality of Vitis vinifera L. cv. Cabernet Gernischt wine.

In some wine regions of China, Cabernet Gernischt (CG; Vitis vinifera L.) grape berries usually exhibit low pigment content and titratable acidity, and low sensory quality of the resulting wine. The aim of this study was to evaluate co-winemaking of CG wines using the red grape cultivar Beibinghong (BBH; Vitis amurensis Rupr.) at different proportions in terms of alcohols, phenolic compounds, and sensory properties of the wines. The results showed that the co-winemaking wines contained a similar content of higher alcohols, whereas the methanol content increased with an increase in BBH proportion, although this was still corresponded with the national standard. Significantly higher levels of titratable acidity were observed in co-winemaking wines at the ratio of 6:4 and 5:5, compared with monocultivar CG wines. All co-winemaking wines, except CG:BBH (9:1) wine, showed significantly higher levels of total anthocyanins, total phenolics, total tannins, and total flavan-3-ols. Further, individual phenolics, primarily diglucoside anthocyanins and non-anthocyanins (trans-ferulic acid, myricetin, viniferin, trans-caffeic acid, 3,4-dihydroxybenzoic acid), as important contributors to wine color intensity, permitted the differentiation of the wines via principal component analysis. In most cases, co-winemaking wines exhibited higher scores of the 10 sensory attributes on color, aroma, mouthfeel, and overall quality compared with monocultivar wines. Co-winemaking CG wines with BBH at 7:3 ratio demonstrated the highest scores of color intensity, aroma intensity, aroma quality, and overall quality. The results indicate that co-winemaking with V. amurensis grape variety may be useful to enhance V. vinifera wine quality by modifying wine composition. PRACTICAL APPLICATION: Cabernet Gernischt (CG) is the predominant grape cultivar used to prepare premium-quality wine in China; however, in some wine regions, CG wines have low levels of pigment and titratable acidity, and low sensory quality. Co-winemaking with another native grape cultivar, Beibinghong (BBH), which is characterized by a higher content of anthocyanins and acidity, provided sufficient experimental evidence of adjustments in the Vitis vinifera wine composition leading to improved wine sensory quality.

Application of stable isotopic and mineral elemental fingerprints in identifying the geographical originof concentrated apple juice in China.

Food traceability is an important component of food safety and quality. Currently, there is no authentic established technique to identify the origin of concentrated apple juice (CAJ) in China. In this study, the isotopes of δ13C, δ18O and the contents of 32 elements in CAJ from five production areas (BHB, NWR, SCH, LP and YRAR) were determined. The δ13C, δ18O and 28 elements were significantly different (P < 0.05: post-hoc Duncan's test) in the five production areas. PCA, PLS-DA and OPLS-DA were employed for regional classification of samples. The results show that ten key variables (Tl, Se, δ18O, B, Mg, Sr, Nd, Mo, As, and Na) are more relevant for discrimination of the samples. These findings contribute to understanding the variations of stable isotopic and element compositions in Chinese CAJ depending on geographic origins and offer valuable insight into the control of fraudulent labeling regarding the geographic origins of CAJ.

Identification of the active compounds and functional mechanisms of Jinshui Huanxian formula in pulmonary fibrosis by integrating serum pharmacochemistry with network pharmacology.

BACKGROUND: Jinshui Huanxian formula (JHF), a traditional Chinese medicine (TCM), has been demonstrated to attenuate idiopathic pulmonary fibrosis (IPF). The active compounds and underlying mechanisms of JHF, however, are unclear. PURPOSE: The purpose of This study was to aimed to identify the active compounds and pharmacological mechanism of JHF by integrating serum pharmacochemistry with a network pharmacology strategy. METHODS: JHF was orally administered to a rat model with bleomycin (BLM)-induced pulmonary fibrosis (PF). The pharmacodynamic effects and compounds present in the serum were identified. The targets and biological mechanisms of these compounds were revealed using network analysis and validated using in vitro experiments. RESULTS: JHF could significantly ameliorate BLM-induced PF by preventing extracellular matrix collagen deposition. Twenty-seven compounds that were found to be enriched in the serum samples collected 1 h after oral administration with JHF were identified as the candidate active compounds, and their 423 potential targets were identified as JHF targets. primarily related to the advanced glycation and products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway, phosphatidylinositol 3 kinase (PI3K)-protein kinase B (PKB or AKT) signaling pathway, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance, etc. The 423 targets, 1145 IPF-related genes and their overlapped genes were applied to analyze, respectively. The results showed that these genes were primarily related to the advanced glycation end-products-receptor for advanced glycation end-products (AGE-RAGE) signaling pathway, lipid and atherosclerosis pathology, phosphatidylinositol 3 kinase (PI3K)-protein kinase B (PKB or AKT) signaling pathway, and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance. Furthermore, the affinity between serum JHF compounds and the main proteins in the above important pathways was investigated through molecular docking. As a result, Molecular docking analysis showed that, tangeretin, isosinensetin, and peimine were found to could bind to EGFR and AKT, and their inhibitory effect on EGFR and AKT were validated in fibroblast cell induced by transforming growth factor (TGF)TGF-ß. The results indicated that suppression of fibroblast activation by inhibiting the EGFR/PI3K/AKT signaling pathway might be an important mechanism of JHF may to treat PF. CONCLUSION: JHF may suppress fibroblast activation by inhibiting the EGFR/PI3K/AKT signaling pathway to ameliorate PF. Tangeretin, isosinensetin, and peimine may be the active compounds in JHF involved in the treatment of that have therapeutic effects on IPF.

Impact of the Acetaldehyde-Mediated Condensation on the Phenolic Composition and Antioxidant Activity of Vitis vinifera L. Cv. Merlot Wine.

Acetaldehyde is a critical reactant on modifying the phenolic profile during red wine aging, suggesting that the acetaldehyde-mediated condensation can be responsible for the variation of antioxidant activity during the aging of this beverage. The present study employs exogenous acetaldehyde at six levels of treatment (7.86 ± 0.10-259.02 ± 4.95 mg/L) before the bottle aging of Merlot wines to encourage phenolic modification. Acetaldehyde and antioxidant activity of wine were evaluated at 0, 15, 30, 45, 60 and 75 days of storage, while monomeric and polymeric phenolics were analyzed at 0, 30 and 75 days of storage. The loss of acetaldehyde was fitted to a first-order reaction model, the rate constant (k) demonstrated that different chemical reaction happened in wines containing a different initial acetaldehyde. The disappearance of monomeric phenolics and the formation of polymeric phenolics induced by acetaldehyde could be divided into two phases, the antioxidant activity of wine did not alter significantly in the first phase, although most monomeric phenolics vanished, but the second phase would dramatically reduce the antioxidant activity of wine. Furthermore, a higher level of acetaldehyde could shorten the reaction time of the first phase. These results indicate that careful vinification handling aiming at controlling the acetaldehyde allows one to maintain prolonged biological activity during wine aging.