Full composition-wide association study identifies the chemical markers to distinguish different processed camellia oils: Integrating multi-targets with chemometrics.

To identify chemical-markers from hot-pressed, cold-pressed, organic-solvent, aqueous-enzymatic and water extracted camellia oils (HPO, CPO, OSO, AEO, WEO). We report a full composition-wide association study based on GC-MS, LC-MS and 1HNMR. Squalene, ß-amyrin and lupeol were potential-markers in distinguishing different oils through GC-MS. Naringenin, FA 18:1 + 10, undecanedioic acid and tridecanedioic acid exhibited were up-regulated in HPO. 16-Hydroxyhexadecanoic acid, octadecanoic acid and 9-hydroxyoctadecadienoic acid were potential-metabolites in CPO. Characteristic-markers in WEO were hydroquinidine and undecanedioic acid. Gallic acid, hydroquinidine, lichesterylic acid and 7,4'-dihydroxyflavone were biomarkers in AEO. Oleic acid, linoleic acid and triacylglycerols may be potential key markers to distinguish AEO from others via 1HNMR. Finally, Naringenin, gallic acid, kaempferol, 7,4'-dihydroxyflavone, (Z)-5,8,11-trihydroxyoctadec-9-enoic acid and ß-amyrin were screened and validate through integration of nonglyceride minor components and trace metabolites. Results provided understanding of chemical diversity for different processed-camellia oils, and proposed a complementary strategy to distinguish different camellia oils for multidimensional perspective.

Characterization and antioxidant properties of three exopolysaccharides produced by the Cyclocarya paliurus endophytic fungus.

In recent years, the considerable potential of endophytic bacteria and fungi as prolific producers of exopolysaccharides (EPSs) have attracted interest. In this study, 56 endophytes were isolated from Cyclocarya paliurus, and the secondary metabolites of EPSs were extracted from Monascus purpureus, Penicillium citrinum and Aspergillus versicolor, screened, and named MPE, PCE and AVE, respectively. In this work, the physicochemical properties and antioxidant activities of three EPSs, their cell proliferation activity on IEC-6 and RAW264.7 were investigated. The three EPSs were mainly composed of neutral sugar and differ in microstructure. However, MPE had a loose structure, and PCE exhibited a dense and sheet-like structure. In addition, the three EPSs performed ordinary antioxidant activity in vitro but showed excellent cell proliferation activity on IEC-6 and RAW264.7. The cell proliferation activity of PCE was 1.4-fold that of the controls at a concentration of 800 µg/mL on IEC-6, and MPE exhibited 1.3-fold increase on RAW264.7. This study provided scientific evidence and insights into the application of endophytes as a novel plant resource possessing huge application potential.

Update on poly(ADP-ribose) polymerase inhibitors resistance in ovarian cancer.

Ovarian cancer is one of the most common reproductive system tumors. The incidence of ovarian cancer in China is on the rise. Poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) is a DNA repair enzyme associated with DNA damage repair. PARPi takes PARP as a target to kill tumor cells, especially for tumors with homologous recombination (HR) dysfunction. Currently, PARPi has been widely used in clinical practice, mainly for the maintenance of advanced ovarian epithelial cancer. The intrinsic or acquired drug resistance of PARPi has gradually become an important clinical problem with the wide application of PARPi. This review summarizes the mechanisms of PARPi resistance and the current progress on PARPi-based combination strategies.

Effect of Mg Contents on the Microstructure, Mechanical Properties and Cytocompatibility of Degradable Zn-0.5Mn-xMg Alloy.

The effect of magnesium (Mg) content on the microstructure, mechanical properties, and cytocompatibility of degradable Zn-0.5Mn-xMg (x = 0.05 wt%, 0.2 wt%, 0.5 wt%) alloys was investigated. The microstructure, corrosion products, mechanical properties, and corrosion properties of the three alloys were then thoroughly characterized by scanning electron microscopy (SEM), electron back-scattered diffraction (EBSD), and other methods. According to the findings, the grain size of matrix was refined by the addition of Mg, while the size and quantity of Mg2Zn11 phase was increased. The Mg content could significantly improve the ultimate tensile strength (UTS) of the alloy. Compared with the Zn-0.5Mn alloy, the UTS of Zn-0.5Mn-xMg alloy was increased significantly. Zn-0.5Mn-0.5Mg exhibited the highest UTS (369.6 MPa). The strength of the alloy was influenced by the average grain size, the solid solubility of Mg, and the quantity of Mg2Zn11 phase. The increase in the quantity and size of Mg2Zn11 phase was the main reason for the transition from ductile fracture to cleavage fracture. Moreover, Zn-0.5Mn-0.2Mg alloy showed the best cytocompatibility to L-929 cells.

Exploring correlations between green coffee bean components and thermal contaminants in roasted coffee beans.

This study evaluated chemical compositions of green coffee beans from multi-production regions and correlated this information with thermal contaminants in roasted coffee. Using multivariate statistical techniques, formation of 5-hydroxymethylfurfural (5-HMF), furan, 2- and 3-methylfuran were positively correlated with lipid, sucrose, glutamic acid, phenylalanine, margaric acid, linolenic acid and trigonelline in green coffee beans. Moreover, significant positive correlations between acrylamide (AA) levels with aspartic acid, serine, alanine, histidine, asparagine, protein, and caffeine was found in green beans. Despite this, 5-HMF, furan, 2- and 3-methylfuran showed negative correlations with active constitutes (neochlorogenic acid, cryptochlorogenic acid, caffeine, total phenolics (TPC) and total flavonoids contents (TFC)), and several amino acids, and there were slight negative relationships between AA and myristic acid, palmitic acid, chlorogenic acid, sucrose, lipid, TPC and TFC. This study provides valuable enlightenment for the selection of proper coffee beans for production of coffee with high nutrition and low chemical hazardous risks.

Elevated GABRP expression is correlated to the excessive autophagy in intrahepatic cholestasis of pregnancy.

In intrahepatic cholestasis of pregnancy (ICP) patients, high concentrations of bile acids altered the normal maternal-fetal-unit physiological condition and could bring negative influence on placenta functionality. GABRP is the pi subunit of the gamma-aminobutyric acid type A receptor (GABAA) and plays pivotal role in regulating GABAA receptor's physiological function. Here we presented evidence that increased expression of GABRP in parallel with autophagic biomarkers, LC3 and ATG14, in patients with ICP. METHODS: A total of 27 participants, including 18 ICP patients and 9 healthy pregnancies were recruited according to strict inclusion criteria. Placentas of ICP patients and controls were collected immediately after cesarean section before labor onset. GABRP and autophagic markers expression in placenta were investigated by immunohistochemistry (IHC), RT-qPCR, and Western blot. RESULTS: The neonatal birthweight and gestational weeks were significantly lower in severe ICP group, while the hepatic enzymes were elevated in ICP group. Semiquantitative analysis of IHC revealed the AOD of GABRP in severe ICP patients was higher than that in mild ICP patients and control pregnancies. Western blot and RT-qPCR analysis both indicated that the expression of GABRP and ATG14 were significantly elevated in severe ICP patients. Moreover, GABRP was correlated with TBA (r = 0.64, p < 0.05), ATG14 (r = 0.87, p < 0.05), direct bilirubin (r = 0.54, p < 0.05), ALT (r = 0.72, p < 0.05), and AST (r = 0.67, p < 0.05). CONCLUSION: There were elevated expression of GABRP, ATG14 and LC3 in ICP placentas compared with uncomplicated pregnancies. The expression of GABRP was associated with autophagy and was correlated with the TBA levels.

Intermolecular binding of blueberry anthocyanins with water-soluble polysaccharides: Enhancing their thermostability and antioxidant abilities.

This study investigated the protective effect of ß-glucan (BG), konjac glucomannan (KGM) and xanthan gum (XG) on thermo-stability and antioxidant capacities of blueberry anthocyanins (ACN) and their interaction mechanisms. Twenty-six glycosylated and acylated ACN were identified, and malvidin-3-O-galactose was predominant (36.78 %) in ACN extracts. Three polysaccharides retained colour and stability and antioxidant capabilities of ACN under thermal-treatments (XG > KGM > BG). Rheological properties (shear stress, apparent viscosity) of three polysaccharides were enhanced in presence of ACN. UV-visible spectra, SEM and DLS results indicated that co-aggregation between ACN and specific zones of these polysaccharides was formed. TGA and DSC studies confirmed that introductionof three polysaccharides, especially XG could improve thermostability of ACN. FTIR, and molecular dynamics simulations revealed that thermo-stabilization of polysaccharides-ACN conjugates might be attributedto their intermolecular interactions mainly via hydrogen bindings. The protection by water-soluble polysaccharides foresees novel anthocyanins in food products with increased heat-resistant stability.

Natural variation on free, esterified, glycosylated and insoluble-bound phenolics of Rubus chingii Hu: Correlation between phenolic constituents and antioxidant activities.

This study sought to determine how the variation of soluble free phenolics (SFPs), soluble-bound (including esterified-bound phenolics (EBPs), glycosylated-bound phenolics (GBPs)) and insoluble-bound phenolics (ISBPs) affected the antioxidant properties (radical scavenging activities and oxidative damage caused by H2O2 in RAW264.7 cell) of Rubus chingii Hu during different maturity stages. Our result demonstrated that the young fruit stage could be considered as a proper harvesting period for Rubus chingii Hu to obtain high antioxidant activities. Distinct tendencies about abundance were found in four phenolic forms and followed the order: SFPs ≈ EBPs > GBPs ≈ IBPs, and antioxidant activities correlation: EBPs > GBPs > SFPs. Furthermore, total phenolic content, total flavonoid content and phenolics such as kaempferol-3-O-rutinoside, tiliroside and ellagic acid have a substantial correlation with antioxidant capacity. This study may supply a theoretical foundation for the utilization and exploitation of Rubus chingii Hu in different maturity periods.

Physicochemical Characteristics of Soluble Dietary Fiber Obtained from Grapefruit Peel Insoluble Dietary Fiber and Its Effects on Blueberry Jam.

Appropriate modification methods can increase the proportion of soluble dietary fiber (SDF). In this study, grapefruit peel insoluble dietary fiber (GP-IDF) was modified with the combined microwave and enzymatic method to obtain SDF. With regard to structural characterization, SDF from grapefruit peel IDF (GP-IDF-SDF) presented as a flat sheet with cracks, composed of a typical cellulose type I crystal, and had good stability below 200 °C. Galacturonic acid, arabinose and glucuronic acid were the main monosaccharide compositions, indicating that pectin might have been the principal component. Moreover, GP-IDF-SDF was excellent in water retention capacity (13.43 ± 1.19 g/g), oil retention capacity (22.10 ± 0.85 g/g) and glucose adsorption capacity (14.49 ± 0.068 mg/g). Thereafter, the effects of GP-IDF-SDF and commercial pectin addition on the color, rheology, texture and sensory properties of blueberry jam were compared. The results showed that the color of jam with GP-IDF-SDF was lighter. The addition of GP-IDF-SDF had less effects on the viscosity and gel strength of jam, but it enhanced the stability of jam. According to sensory data, the color, texture and spreadability of jam with GP-IDF-SDF or pectin were improved and more acceptable. Overall, GP-IDF-SDF had functional characteristics and played a positive role in jam, and it is expected to be a candidate for the development of functional food ingredients.

Assessing the Prognostic Capability of Immune-Related Gene Scoring Systems in Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is the commonest of the subtypes of lung cancer histologically. For this study, we intended to analyze the expression profiling of the immune-related genes (IRGs) from an independently available public database and developed a potent signature predictive of patients' prognosis. Methods: Gene expression profiles and the clinical data of lung adenocarcinoma were gathered from the Gene Expression Omnibus database (GEO) and The Cancer Genome Atlas (TCGA), and the obtained data were split into a training set (n = 226), test set (n = 83), and validation set (n = 400). IRGs were then gathered from the ImmPort database. A prognostic model was constructed by analyzing the training set. Then the GO and KEGG analysis was performed, and a gene correlation prognostic nomogram was constructed. Finally, external validation, such as immune infiltration and immunohistochemistry, was performed. Results: The 110 genes were significant by univariate Cox regression analysis and randomized survival forest algorithm for the training set and showed a good distinction between the low-risk-score and high-risk-score groups in the training set (P < 0.0001) by screening for four prognosis-related genes (HMOX1, ARRB1, ADM, PDIA3) and validated by the test set GSE30219 (P=0.0025) and TCGA dataset (P=0.00059). Multivariate Cox showed that the four gene signatures were an individual risk factor for LUAD. In addition, the genes in the signatures were externally verified using an online database. In particular, PDIA3 and HMOX1 are essential genes in the prognostic nomogram and play an important role in the model of immune-related genes. Conclusion: Four immune-related genetic signatures are reliable prognostic indicators for patients with LUAD, providing a relevant theoretical basis and therapeutic rationale for immunotherapy.

Catabolism of polyphenols released from mung bean coat and its effects on gut microbiota during in vitro simulated digestion and colonic fermentation.

Mung bean coat is a good source of dietary polyphenols. In this study,in vitro simulated digestion and colonic fermentation were performed to investigate the release of polyphenols from mung bean coat and their bioactivities. Polyphenols released by colonic fermentation were much higher than those released by digestion and reached a peak at 12 h, resulting in higher antioxidant capacities (DPPH, ORAC, FRAP assays). About 49 polyphenols and metabolites including quercetin, vanillin, catechin and p-hydroxybenzoic acid were identified, and possible biotransformation pathways were postulated. Moreover, the relative abundance of beneficial bacteria (such as Lactococcus and Bacteroides) was improved during colonic fermentation. Altogether, gut microbiota could release polyphenols, the released polyphenols and their catabolic metabolites, alongside dietary fiber in mung bean coat selectively regulated the composition of gut microbiota and promoted the synthesis of SCFAs. These findings indicated that polyphenols in mung bean coat potentially contributed to gastrointestinal and colonic health.

Mixed solid-state fermentation for releasing bound polyphenols from insoluble dietary fiber in carrots via Trichoderma viride and Aspergillus niger.

This study aimed to explore the release mechanism of bound polyphenols (BP) from the insoluble dietary fiber (IDF) in carrots via mixed solid-state fermentation (MSF) using Trichoderma viride and Aspergillus niger. The results indicated that BP released by MSF (80.8759 mg GAE per 10 g DW) was significantly higher than that by alkaline hydrolysis. In addition, 17 polyphenols were detected and their biotransformation pathways were proposed. Quantitative analysis showed that MSF released numerous p-coumaric and organic acids, which led to both an enhancement in α-amylase inhibitory activity and elevated antioxidant enzyme activity in Caenorhabditis elegans (C. elegans). Furthermore, the dynamic changes in the carbohydrate-hydrolyzing enzymes and the structural characteristics indicated that the destruction of hemicellulose, the deposition of lignin and the secretion of xylanase were vital for the release of BP. Overall, this study demonstrated that MSF is beneficial for the release of BP from IDF, which could provide new insight into the utilization of agricultural byproducts in a more natural and economical way.

Single cell RNA sequencing research in maternal fetal interface.

The maternal-fetal interface is an essential environment for embryonic growth and development, and a successful pregnancy depends on the dynamic balance of the microenvironment at the maternal-fetal interface. Single-cell sequencing, which unlike bulk sequencing that provides averaged data, is a robust method for interpreting the cellular and molecular landscape at single-cell resolution. With the support of single-cell sequencing, the issue of maternal-fetal interface heterogeneity during pregnancy has been more deeply elaborated and understood, which is important for a deeper understanding of physiological and pathological pregnancy. In this paper, we analyze the recent studies of single-cell transcriptomics in the maternal-fetal interface, and provide new directions for understanding and treating various pathological pregnancies.

Current understanding of autophagy in intrahepatic cholestasis of pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease during pregnancy. Manifested with pruritus and elevation in bile acids, the etiology of ICP is still poorly understood. Although ICP is considered relatively benign for the mother, increased rates of adverse fetal outcomes including sudden fetal demise are possible devastating outcomes associated with ICP. Limited understanding of the underlying mechanisms restricted treatment options and managements of ICP. In recent decades, evolving evidence indicated the significance of autophagy in pregnancy and pregnancy complications. Autophagy is an ancient self-defense mechanism which is essential for cell survival, differentiation and development. Autophagy has pivotal roles in embryogenesis, implantation, and maintenance of pregnancy, and is involved in the orchestration of diverse physiological and pathological cellular responses in patients with pregnancy complications. Recent advances in these research fields provide tantalizing targets on autophagy to improve the care of pregnant women. This review summarizes recent advances in understanding autophagy in ICP and its possible roles in the causation and prevention of ICP.

The recovery, catabolism and potential bioactivity of polyphenols from carrot subjected to in vitro simulated digestion and colonic fermentation.

Carrot powder digestion was researched utilizing an in vitro standardized static model associated with an in vitro colonic fermentation method to analyze the recovery, catabolism, and potential bioactivity of polyphenols from carrot. Twenty-seven polyphenols and their metabolites (hydroxybenzoic acids, hydroxycinnamic acids and its derivatives, etc.) were identified in samples before and after digestion/colonic fermentation, and the possible colonic pathways for major polyphenols were proposed. Polyphenols had low recovery during different phases of in vitro digestion (oral: -51.4%; gastric: -38%; intestinal: -35.3%, respectively). However, the concentration of polyphenols (p-hydroxybenzoic acid, gallic acid and protocatechuic acid) increased significantly after colonic fermentation for 12 h with 1391.7% recovery, then significantly declined after 48 h. Meanwhile, the released and catabolized polyphenols showed antioxidant activity and α-glucosidase inhibitory capacity (IC50 = 9.91 µg GAE/mL). The microbe community structure was regulated by fecal fermented carrot powder through improving relative abundance (RA) of beneficial microbiota and suppressed RA of various harmful bacteria. This work indicated that polyphenols from carrot potentially play a role in gastrointestinal and colonic health.

Bound Polyphenols from Insoluble Dietary Fiber of Defatted Rice Bran by Solid-State Fermentation with Trichoderma viride: Profile, Activity, and Release Mechanism.

This study is aimed at exploring the release of bound polyphenols (BP) from insoluble dietary fiber (IDF) and its mechanism by solid-state fermentation (SSF) via Trichoderma viride. The results indicated that BP released by SSF (5.55 mg GAE/g DW) was significantly higher than by alkaline hydrolysis. In addition, 39 polyphenols and catabolites were detected, and the related biotransformation pathways were speculated. Quantitative analysis showed that SSF released more ferulic acid, p-coumaric acid, and organic acids, which led to advances in antioxidant, α-amylase, and α-glucosidase inhibitory activities. Furthermore, structural characteristics (scanning electron microscopy, X-ray diffraction, thermos gravimetric analysis, and Fourier transform infrared spectroscopy) and dynamic changes of carbohydrate-hydrolyzing enzymes indicated that the destruction of hemicellulose and the secretion of xylanase were vital for releasing BP. Overall, this study demonstrated that SSF was beneficial to release BP from IDF, which could provide insight into utilizing agricultural byproducts in a more natural and economical way.

Composition of bound polyphenols from carrot dietary fiber and its in vivo and in vitro antioxidant activity.

Qualitative analysis of bound polyphenols from carrot dietary fiber (CDF-PP) was performed by ultra-performance liquid chromatography equipped with an electrospray ionization and quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS/MS). Eleven organic acids, nine hydroxybenzoic acids and derivatives, six hydroxycinnamic acids and derivatives, four phenolic alcohols and derivatives, three flavonoids and derivatives, seven esters and derivatives, two other compounds, were detected by matching their retention times, secondary mass spectrometry fragment information with authentic standards or literature data. Furthermore, in vitro antioxidant activity was determined by different kinds of assays, including DPPH, ORAC, PSC, demonstrated that CDF-PP could scavenge radicals in a dose dependent manner. Moreover, CDF-PP exhibited significantly reactive oxygen species (ROS) scavenging activity in living Caenorhabditis elegans. To our knowledge, this is the first comprehensive research to investigate composition and in vitro/in vivo antioxidant activity of bound polyphenols in CDF, which implied that CDF-PP could be a promising source of antioxidants.

Circulating Irisin Level and Thyroid Dysfunction: A Systematic Review and Meta-Analysis.

Both thyroid hormones and irisin have profound influences on the metabolism of the human body. Based on their similarities, several studies have been conducted to explore changes in irisin levels in patients with hypothyroidism and hyperthyroidism. This study was conducted in accordance with the PRISMA statement and the MOOSE reporting guideline. Based on a preregistered protocol (PROSPERO-CRD42019138430), a comprehensive search of eight databases was performed from inception to April 2020. Studies with original data collected from patients with thyroid dysfunction were included. Subgroup analysis was performed based on the different types of clinical manifestations and patient characteristics. The quality of each study and the presence of publication bias were assessed by the Newcastle-Ottawa score (NOS) and funnel plot with Egger's test, respectively. A total of 11 studies with 1210 participants were included. Ten studies were identified as high-quality studies. Pooled analysis indicated decreased irisin levels in patients with hypothyroidism (MD -10.37, 95% CI -17.81 to -2.93). Subgroup analysis revealed an even lower level of irisin in patients with clinical-type hypothyroidism (MD -17.03, 95% CI -30.58 to -3.49) and hypothyroidism caused by autoimmune disease (MD -19.38, 95% CI -36.50 to -2.26). No differences were found after achieving euthyroid status from levothyroxine treatment in patients with hypothyroidism compared with controls. No differences were found between patients with hyperthyroidism and controls. Correlation analyses revealed a possible negative correlation between irisin and TSH and positive correlations between irisin and both fT3 and fT4. Irisin was correlated with TSH receptor antibodies.

Release and metabolism of bound polyphenols from carrot dietary fiber and their potential activity in in vitro digestion and colonic fermentation.

Dietary fiber is a carrier of abundant polyphenols and the potential benefits have attracted increasing attention. In this study, we performed in vitro simulated digestion in the oral, gastric and intestinal phases, and colonic fermentation with human fecal microbes, to explore the release and metabolism of bound polyphenols from carrot dietary fiber (CDF) and the potential activity. The results indicate that the bound polyphenols released by the fecal fermentation process (30.43%) from CDF were higher than in the digestion process (0.89%); 26 polyphenols and their catabolites were detected and the microbial pathways of primary polyphenols were proposed. The significant disintegration of the sheet-like structure of CDF after the in vitro fermentation was comparable to that of the digestion treatment. The released polyphenols exhibited antioxidant capacity and α-glucosidase inhibitory activity. The microbe community structure was regulated by the fecal-fermented CDF through decreasing the Firmicutes to Bacteroidetes ratio, improving the relative abundance (RA) of the beneficial microbiota and suppressing the RA of various harmful microbiota. Overall, this study suggests that the bound polyphenols might exert potential benefits in the gastrointestinal and colonic health of the CDF.

The effect of bound polyphenols on the fermentation and antioxidant properties of carrot dietary fiber in vivo and in vitro.

Growing attention has been paid to the importance of bound polyphenols in dietary fiber. This study aimed to elucidate the effect of bound polyphenols on the fermentation and antioxidant properties of carrot dietary fiber (CDF) in vivo and in vitro. Compared with CDF treatment, 16S rRNA pyrosequencing of in vivo mice feces and in vitro human fecal fermentation samples showed that dephenolized carrot dietary fiber (CDF-DF) treatment decreases operational taxonomic units (OTUs), ACE and Chao1 indexes, increases Firmicute/Bacteroidetes ratio and relative abundance (RA) of Parabacteroides at phylum, restrains RAs of typical beneficial bacteria as well as improves RAs of various harmful bacteria at genus. Meanwhile, short-chain fatty acid (SCFA) contents were lower, while the pH value was higher in the CDF-DF group than those in the CDF group. Interestingly, the combination of bound polyphenols and CDF-DF (CDDP) could recover these indexes influenced by the removal of bound polyphenols in in vitro fermentation samples. Furthermore, the CDF-DF-fed mice exhibited higher MDA content and lower SOD and GSH-Px activities in the colon. The cellular antioxidant activity (CAA) value of CDF-DF was lower than that of CDF and CDDP. These results revealed that bound polyphenols significantly contribute to the fermentation and antioxidant properties of CDF.