Interpretable machine learning-based clinical prediction model for predicting lymph node metastasis in patients with intrahepatic cholangiocarcinoma.

OBJECTIVE: Prediction of lymph node metastasis (LNM) for intrahepatic cholangiocarcinoma (ICC) is critical for the treatment regimen and prognosis. We aim to develop and validate machine learning (ML)-based predictive models for LNM in patients with ICC. METHODS: A total of 345 patients with clinicopathological characteristics confirmed ICC from Jan 2007 to Jan 2019 were enrolled. The predictors of LNM were identified by the least absolute shrinkage and selection operator (LASSO) and logistic analysis. The selected variables were used for developing prediction models for LNM by six ML algorithms, including Logistic regression (LR), Gradient boosting machine (GBM), Extreme gradient boosting (XGB), Random Forest (RF), Decision tree (DT), Multilayer perceptron (MLP). We applied 10-fold cross validation as internal validation and calculated the average of the areas under the receiver operating characteristic (ROC) curve to measure the performance of all models. A feature selection approach was applied to identify importance of predictors in each model. The heat map was used to investigate the correlation of features. Finally, we established a web calculator using the best-performing model. RESULTS: In multivariate logistic regression analysis, factors including alcoholic liver disease (ALD), smoking, boundary, diameter, and white blood cell (WBC) were identified as independent predictors for LNM in patients with ICC. In internal validation, the average values of AUC of six models ranged from 0.820 to 0.908. The XGB model was identified as the best model, the average AUC was 0.908. Finally, we established a web calculator by XGB model, which was useful for clinicians to calculate the likelihood of LNM. CONCLUSION: The proposed ML-based predicted models had a good performance to predict LNM of patients with ICC. XGB performed best. A web calculator based on the ML algorithm showed promise in assisting clinicians to predict LNM and developed individualized medical plans.

IL4I1 enhances PD-L1 expression through JAK/STAT signaling pathway in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the major type of lung cancer and is one of the deadliest cancers worldwide. IL4I1, as a gene associated with unsatisfactory prognosis, is involved in tumor immune escape, but its immune regulatory mechanism in LUAD is limited. Bioinformatics analysis was applied to analyze the differentially expressed mRNAs and enriched signaling pathways in LUAD tissue. Quantitative real-time polymerase chain reaction (qRT-PCR) was manipulated to test IL4I1 expression. We carried out several methods to examine cell functions: CCK-8 to measure LUAD cell proliferation; flow cytometry to determine cell apoptosis; Western blot to assess the expression of JAK/STAT pathway-related proteins and PD-L1; T cell cytotoxicity assay to evaluate the effect of IL4I1 on the immune escape of LUAD cells. Through bioinformatics analysis, IL4I1 was verified to be highly expressed in LUAD tissue, participate in the modulation of JAK/STAT signaling pathway, and be positively associated with CD274 (PD-L1) expression. Cell function experiments indicated that silencing IL4I1 notably repressed LUAD cell proliferation and induced apoptosis. IL4I1 silence would block JAK/STAT signaling pathway, but this effect could be reversed by RO8191 activator treatment. Moreover, IL4I1 silence suppressed PD-L1 expression and facilitated T cell cytotoxicity, while its inhibitory impact on PD-L1 expression and immune escape of LUAD cells could be reversed by atezolizumab treatment. Overall, we confirmed that IL4I1 promoted the malignant cell behaviors and immune escape of LUAD through JAK/STAT signaling pathway. IL4I1 has the potential to be a diagnostic biomarker for LUAD.

Supramolecular Structure and Photo-Thermo-Electric Property of Hydrogen-Bonded Liquid Crystalline Polymer Containing Poly(4-vinylpridine) and Cyanostilbene Side Chains.

A series of side-chain liquid crystalline polymers P4VP(CN-DBE)x , where x is the molar ratio of cyanostilbene (CN-DBE) to poly(4-vinylpyridine) (P4VP) repeating unit, was synthesized based on the intermolecular hydrogen bonding between P4VP and CN-DBE. Their luminescent property, liquid crystalline structure and photo-thermo-electric property were elucidated using photoluminescence spectra, X-ray diffraction, thermal imaging and thermoelectric experiments. With the increase of x, the supramolecular system can be changed from lamellar structure to hexagonal columnar structure. Moreover, the P4VP(CN-DBE)x polymer with columnar structure exhibits more efficient photothermal effect. The temperature of P4VP(CN-DBE)0.6 can rise to 130 °C within 10 s under the irradiation of ultraviolet lamp. In addition, the supramolecular system possesses unique photo-thermo-electric conversion ability, and 25 mA current can be detected in the circuit coupled with the thermoelectric module. This work broadens the potential applications of hydrogen-bonded polymer, and provides a simple and facile strategy to prepare liquid crystalline polymers with photo-thermo-electric property.

A Fast Sparse Decomposition Based on the Teager Energy Operator in Extraction of Weak Fault Signals.

In order to diagnose an incipient fault in rotating machinery under complicated conditions, a fast sparse decomposition based on the Teager energy operator (TEO) is proposed in this paper. In this proposed method, firstly, the TEO is employed to enhance the envelope of the impulses, which is more sensitive to frequency and can eliminate the low-frequency harmonic component and noise; secondly, a smoothing filtering algorithm was adopted to suppress the noise in the TEO envelope; thirdly, the fault signal was reconstructed by multiplication of the filtered TEO envelope and the original fault signal; finally, sparse decomposition was used based on a generalized S-transform (GST) to obtain the sparse representation of the signal. The proposed preprocessing method using the filtered TEO can overcome the interference of high-frequency noise while maintaining the structure of fault impulses, which helps the processed signal perform better on sparse decomposition; sparse decomposition based on GST was used to represent the fault signal more quickly and more accurately. Simulation and application prove that the proposed method has good accuracy and efficiency, especially in conditions of very low SNR, such as impulses with anSNR of -8.75 dB that are submerged by noise of the same amplitude.

miR-198 inhibits the progression of renal cell carcinoma by targeting BIRC5.

BACKGROUND: miR-198 is involved in the formation, migration, invasion, and metastasis of various malignant cancers. However, the function and mechanism of action of miR-198 in the tumorigenesis of renal cell carcinoma (RCC) remain elusive. Here, we aimed to explore the role of miR198 in RCC. METHODS: Immunohistochemistry was performed to estimate the level of survivin in RCC sections. Quantitative real-time polymerase chain reaction was performed to determine the expression level of miR-198 in fresh RCC tissues. Furthermore, the target relationship between miR-198 and BIRC5 was predicted using the TargetScanHuman 7.2 database and verified via dual-luciferase reporter assay and western blotting. The effects of miR-198 on the viability, apoptosis, invasion, and migration of A498 and ACHN cells were studied using Cell Counting Kit-8, flow cytometry, transwell migration assay, and wound healing assay, respectively. Additionally, a xenograft nude mouse model was established to evaluate the effect of miR-198 on RCC tumorigenesis. RESULTS: The expression levels of BIRC5 and miR-198 were respectively higher and lower in RCC tissues than those in normal adjacent tissues. Furthermore, miR-198 could inhibit luciferase activity and reduce the protein level of survivin without affecting the BIRC5 mRNA levels. miR-198 inhibited cell viability, migration, and invasion and promoted cell apoptosis; co-transfection with BIRC5 could rescue these effects. Moreover, miR-198 could repress tumor growth in the xenograft nude mouse model of RCC. CONCLUSIONS: Our study demonstrates that miR-198 suppresses RCC progression by targeting BIRC5.

The prevalence, relative risk factors and MTHFR C677T genotype of H type hypertension of the elderly hypertensives in Shanghai, China: a cross-section study : Prevalence of H type hypertension.

BACKGROUND: H type hypertension is defined as homocysteine (Hcy) ≥ 10 µmol/L in combination with primary hypertension. Studies demonstrated that the existence of hyperhomocysteine (HHcy) in hypertensive exacerbates the poor outcome of cardiocerebral incidents. This study was to investigate the current epidemic situation of H type hypertension and determine the risk factors in order to find intervention targets for H type hypertensives. METHODS: We conducted a cross-sectional study using cluster sampling design in Shanghai, China from July 2019 and April 2020. 23,652 patients with primary hypertension were enrolled in this study. Their medical information was recorded, and the level of Hcy concentrations and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms were detected. RESULTS: In total, 22,731 of 23,652 patients were recorded. The mean age was 68.9 ± 8.6 y and 43% were men. 80.0% of the enrolled patients had H type hypertension. The frequency of allele T was 40.9%, and the proportions of the CC, CT, and TT genotypes were 36.1%, 46.0%, and 17.9%, respectively. Compared with the TT genotype, the plasma Hcy concentration levels were lower in patients with the CC/CT genotype (18.96 ± 13.48 µmol/L vs. 13.62 ± 5.20/14.28 ± 5.36, F = 75.04, p < 0.01). The risk for H type hypertension was higher in elderly people. Men had ~ 5.55-fold odds of H type hypertension compared with women. Patients with CT genotype and TT genotype had ~ 1.36- and ~ 2.76-fold odds of H type hypertension compared with those with CC genotype, respectively. Smoking and diabetes were not significantly associated with H type hypertension. CONCLUSIONS: The prevalence of H type hypertension in patients with primary hypertension was 80.0%, which was higher than the 75% found in prior report in China. Age, gender, and MTHFR C677T polymorphisms rather than smoking and diabetes were independently associated with H type hypertension.

Design, synthesis and in vitro anticancer research of novel tetrandrine and fangchinoline derivatives.

Cancer treatment is one of the major public health issues in the world. Tetrandrine (Tet) and fangchinoline (d-Tet) are two bis-benzyl isoquinoline alkaloids extracted from Stephania tetrandra S. Moore, and their antitumor activities have been confirmed. However, the effective dose of Tet and d-Tet were much higher than that of the positive control and failed to meet clinical standards. Therefore, in this study, as a continuation of our previous work to study and develop high-efficiency and low-toxic anti-tumor lead compounds, twenty new Tet and d-Tet derivatives were designed, synthesized and evaluated as antitumor agents against six cancer cell lines (H460, H520, HeLa, HepG-2, MCF-7, SW480 cell lines) and BEAS-2B normal cells by CCK-8 analysis. Ten derivatives showed better cytotoxic effects than the parent fangchinoline, of which 4g showed the strongest cell growth inhibitory activity with an IC50 value of 0.59 µM against A549 cells. Subsequently, the antitumor mechanism of 4g was studied by flow cytometry, Hoechst 33258, JC-1 staining, cell scratch, transwell migration, and Western blotting assays. These results showed that compound 4g could inhibit A549 cell proliferation by arresting the G2/M cell cycle and inhibiting cell migration and invasion by reducing MMP-2 and MMP-9 expression. Meanwhile, 4g could induce apoptosis of A549 cells through the intrinsic pathway regulated by mitochondria. In addition, compound 4g inhibited the phosphorylation of PI3K, Akt and mTOR, suggesting a correlation between blocking the PI3K/Akt/mTOR pathway and the above antitumor activities. These results suggest that compound 4g may be a future drug for the development of new potential drug candidates against lung cancer.

Exploring core functional microbiota responsible for the production of volatile flavour during the traditional brewing of Wuyi Hong Qu glutinous rice wine.

The objective of this study was to explore the core functional microbiota for the production of volatile flavour during the traditional brewing of Wuyi Hong Qu glutinous rice wine, one of the most typical representatives of rice wine in China. Microbiological analysis based on high-throughput sequencing (HTS) technology demonstrated that bacteria of Lactobacillus, Bacillus, Leuconostoc, Lactococcus, Raoultella, Staphylococcus, Pediococcus, and Weissella, and fungi of Saccharomyces, Saccharomycopsis, Rhizopus, Monascus, Pichia, Wickerhamomyces, Candida, and Aspergillus were the predominant genera during the traditional fermentation process. Principal component analysis (PCA) based on the relative abundance showed that both of bacterial and fungal communities varied significantly in different fermentation phases. Some predominant microbial species or genera (including bacteria of Bacillus spp., Staphylococcus spp., Weissella spp., and P. acidilactici, and fungi of M. purpureus, R. oryzae, R. arrhizus var. arrhizus, and A. niger) were detected at the initial brewing stage, and their populations decreased as the fermentation progressed, while those of Lactobacillus, Gluconacetobacter, Leuconostoc, Pichia, Wickerhamomyces, and Saccharomyces increased to become the predominant genera at the final stage. A total of 79 volatile compounds were identified in traditional fermentation starters and during the traditional brewing process, mainly including esters, alcohols, acids, aldehydes, ketones, and phenols. Heatmaps and PCA also revealed the significant variances in the composition of volatile compounds among different samples. Furthermore, the potential correlations between microbiota succession and volatile flavour dynamics were explored through bidirectional orthogonal partial least squares (O2PLS) based correlation analysis. Three bacterial genera, namely, Gluconacetobacter, Lactobacillus, Lactococcus, and three fungal genera of Pichia, Wickerhamomyces, and Saccharomyces, were determined as the core functional microbiota for production of main volatile compounds in Wuyi Hong Qu glutinous rice wine. To conclude, information provided by this study is valuable to the development of effective strategies for the selection of beneficial bacterial and fungal strains to improve the quality of Wuyi Hong Qu glutinous rice wine.

Antitumor evaluation and multiple analysis on different extracted fractions of the root of Cynanchum auriculatum Royle ex Wight.

The root of Cynanchum auriculatum (C. auriculatum) Royle ex Wight has been shown to possess various pharmacological effects and has recently attracted much attention with respect to its potential role in antitumor activity. The C-21 steroidal glycosides are commonly accepted as the major active ingredients of C. auriculatum. In this study, the antitumor abilities of different extracted fractions of the root bark and the root tuber of C. auriculatum were investigated by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in human cancer cell lines HepG2 and SMMC-7721. The results showed that the chloroform and ethyl acetate fractions of the root tuber suppressed tumor cell growth strongly. To identify and characterize the chemical constituents of different active fractions, an ultra high performance liquid chromatography with triple-quadrupole tandem mass spectrometry method was developed for the simultaneous quantitation of eight C-21 steroidal glycosides. The analysis revealed that the C-21 steroidal glycosides were concentrated in the chloroform and ethyl acetate fractions, and the total contents of different fractions in the root tuber were significantly higher than those of corresponding ones in the root bark. Furthermore, the C-21 steroidal glycosides based on different types of aglucones were prone in different medicinal parts of C. auriculatum.

Genetic variants in lncRNA H19 are associated with the risk of bladder cancer in a Chinese population.

The long non-coding RNA (lncRNA) H19 as an imprinted gene transcribed from only the maternal allele has the vital role in carcinogenesis. Aberrant H19 expression is involved in bladder cancer development. In this study, we explored the association between single nucleotide polymorphisms (SNPs) in H19 and bladder cancer risk. Four tagging SNPs (tagSNPs) were selected from the 1000 Genomes Project database. In total, 1049 bladder cancer cases and 1399 controls were recruited in this case-control study. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated by using unconditional univariate and multivariate logistic regression models to evaluate associations between the H19 tagSNPs genotypes and risk of bladder cancer. We found a statistically significant increased risk of bladder cancer in the carriers of the rs217727 AA genotype compared with carriers of GG/GA genotype (OR = 1.31, 95% CI = 1.03-1.67). The subsequently stratified analyses also revealed that the H19 rs217727 AA genotype remarkably elevated the risk of bladder cancer in subgroups of young subjects (OR = 1.80, 95% CI = 1.16-2.81), males (OR = 1.44, 95% CI = 1.10-1.89) and smokers (OR = 1.55, 95% CI = 1.06-2.27), as well as high tumour grade (OR = 1.89, 95% CI = 1.23-2.91) and invasive disease (OR = 1.62, 95% CI = 1.01-2.60). This finding indicates that the rs217727 polymorphism is significantly associated with the risk of bladder cancer.

Integrating p53-associated genes and infiltrating immune cell characterization as a prognostic biomarker in multiple myeloma.

Background: Tumor genetic anomalies and immune dysregulation are pivotal in the progression of multiple myeloma (MM). Accurate patient stratification is essential for effective MM management, yet current models fail to comprehensively incorporate both molecular and immune profiles. Methods: We examined 776 samples from the MMRF CoMMpass database, employing univariate regression with LASSO and CIBERSORT algorithms to identify 15 p53-related genes and six immune cells with prognostic significance in MM. A p53-TIC (tumor-infiltrating immune cells) classifier was constructed by calculating scores using the bootstrap-multicox method, which was further validated externally (GSE136337) and through ten-fold internal cross-validation for its predictive reliability and robustness. Results: The p53-TIC classifier demonstrated excellent performance in predicting the prognosis in MM. Specifically, patients in the p53low/TIChigh subgroup had the most favorable prognosis and the lowest tumor mutational burden (TMB). Conversely, those in the p53high/TIClow subgroup, with the least favorable prognosis and the highest TMB, were predicted to have the best anti-PD1 and anti-CTLA4 response rate (40 %), which can be explained by their higher expression of PD1 and CTLA4. The three-year area under the curve (AUC) was 0.80 in the total sample. Conclusions: Our study highlights the potential of an integrated analysis of p53-associated genes and TIC in predicting prognosis and aiding clinical decision-making in MM patients. This finding underscores the significance of comprehending the intricate interplay between genetic abnormalities and immune dysfunction in MM. Further research into this area may lead to the development of more effective treatment strategies.

Diversity of staminal nectariferous appendages in disymmetric and zygomorphic flowers of Fumarioideae (Papaveraceae).

Staminal nectaries show diversity in their position, size, shape, color, and number in Ranunculales. In Papaveraceae, nectaries only appear at the base of stamen in these lineages with disymmetric and zygomorphic flowers. However, the diversity of the staminal nectaries' developmental characteristics and structure is unknown. The diversity of staminal nectaries of Hypecoum erectum, Ichtyoselmis macrantha, Adlumia asiatica, Dactylicapnos torulosa, Corydalis edulis, and Fumaria officinalis (six species belonging to six genera, respectively) in the Fumarioideae was investigated under scanning electron microscopy, light microscopy, and transmission electron microscopy. In all species studied, according to the developmental characteristics of the nectaries, four developmental stages can be divided into initiation, enlargement, differentiation, and maturation, and the number of nectaries can be determined at the stage of initiation (stage 1), and morphological differentiation occurs at the developmental stage 3. The staminal nectaries consist of secretory epidermis, parenchyma tissue, and phloem with some sieve tube elements reaching the secretory parenchyma cells; however, the number of cell layers of parenchyma can vary from 30 to 40 in I. macrantha and D. torulosa, to only 5 to 10 like in F. officinalis. Secretory epidermis cells are larger than secretory parenchyma cells with abundant microchannels on the outer cell wall. There were abundant mitochondria, Golgi bodies, rough endoplasmic reticulum, and plastids in secretory parenchyma cells. Nectar is stored in the intercellular space and exuded to the exterior via microchannels. In A. asiatica, according to the evidence of small secretory cell characteristics such as dense cytoplasm, and numerous mitochondria, together with the filamentous secretions present on the surface of epidermal cells on groove, it can be inferred that the U-shaped sulcate which is located in the white projection formed at the filament of triplets in A. asiatica is nectariferous.

Impact of fuel aromatic content on soot particle physicochemical properties of marine auxiliary diesel engine.

Fuel aromatic content (AC) is one of the main reasons for PM (particulate matter) emissions from ocean-going ships. The present study investigates the influence of AC on physicochemical characteristics of soot particles from marine auxiliary diesel engine. The TEM (transmission electron microscopy), Raman spectroscopy, FTIR (Fourier transform infrared spectroscopy), and TGA (thermalgravimetric analyzer) are employed to jointly characterize samples. The results reveal that soot particles from high-AC fuel have bigger dp (primary particle size), longer fringe length (La), and higher graphitization degree, all of which have significant impacts on chemical properties such as more VOF (volatile organic fraction), higher concentrations of aromatic C-H and C=C groups. These are mainly due to several aromatic rings decomposed from aromatic components could promote the growth of carbon layer, and incomplete pyrolysis productions are also present in soot particles. The relative amounts of aromatic C-H and C=C are well correlated with dp and La, respectively.

Comparative Transcriptomic and Metabolomic Analyses Reveal the Regulatory Effect and Mechanism of Tea Extracts on the Biosynthesis of Monascus Pigments.

Monascus pigments (MPs) are natural edible pigments with high safety and strong function, which have been widely used in food and health products. In this study, different types of tea extracts (rich in polyphenols) were used to regulate the biosynthesis of MPs. The results showed that 15% ethanol extract of pu-erh tea (T11) could significantly increase MPs production in liquid fermentation of Monaco's purpureus M3. Comparative transcriptomic and metabolomic analyses combined with reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to further explore the regulatory mechanism of T11 on the biosynthesis of MPs. Comparative transcriptomic analysis showed that there were 1503 differentially expressed genes (DEGs) between the Con group and the T11 group, which were mainly distributed in carbohydrate metabolism, amino acid metabolism, energy metabolism, lipid metabolism, metabolism of terpenoids and polyketides, etc. A total of 115 differential metabolites (DMs) identified by metabolomics between the Con and T11 groups were mainly enriched in glutathione metabolism, starch and sucrose metabolism, alanine, aspartic acid and glutamate metabolism and glycine, serine and threonine metabolism, etc. The results of metabolomics were basically consistent with those of gene transcriptomics, indicating that the regulatory effect of T11 on the biosynthesis of MPs is mainly achieved through affecting the primary metabolic pathway, providing sufficient energy and more biosynthetic precursors for secondary metabolism. In this study, tea extracts with low economic value and easy access were used as promoters of MPs biosynthesis, which may be conducive to the application of MPs in large-scale industrial production. At the same time, a more systematic understanding of the molecular regulatory mechanism of Monascus metabolism was obtained through multi-omics analysis.

Evaluation of Volatile Profile and In Vitro Antioxidant Activity of Fermented Green Tea Infusion With Pleurotus sajor-caju (Oyster Mushroom).

Green tea has distinct astringency, bitter taste, and typical green flavor because of its post-harvest treatment without withering and enzymatic oxidation. Microbial fermentation has been identified as a promising strategy that could give green tea infusion a special taste flavor. This might be linked to the metabolic transformation ability of microorganisms. In this study, starter culture of edible mushroom Pleurotus sajor-caju (oyster mushroom) was used for submerged fermentation of green tea infusion in order to improve its flavor and taste quality. The volatile profile determined by headspace solid-phase microextraction, coupled with gas chromatography mass spectrometry, showed that the contents of (Z)-2-penten-1-ol and methyl heptadienone in green tea infusion were decreased significantly by the fermentation with the basidiomycete P. sajor-caju (p < 0.01), which would alleviate the herbal and grass flavor of green tea infusion to a certain extent. Meanwhile, the contents of linalool and geraniol were increased 9.3 and 11.3 times, respectively, whereas methyl salicylate was newly produced after fermentation by P. sajor-caju, endowing the fermented tea infusion with a pleasant flower and fruit aroma. In addition, the polyphenol profile was determined using high-performance liquid chromatography equipped with ion trap mass spectrometry, and the results indicated that the contents of most polyphenols in green tea infusion decreased significantly after fermentation by P. sajor-caju. The reduction of catechins and anthocyanins in fermented green tea infusion alleviated the astringency and bitterness. Moreover, the antioxidant activity of fermented green tea infusion was obviously decreased, especially the DPPH-free radical-scavenging ability and the ferric-reducing power. However, it is noteworthy that the ABTS-free radical scavenging ability was improved compared with the unfermented one, indicating that the increased tea pigments and volatile metabolites (such as linalool and geraniol) after fermentation with P. sajor-caju may also contribute to the antioxidant capacity of fermented green tea infusion. Overall, the innovative approach driven by P. sajor-caju fermentation has achieved promising potential to manipulate the green tea flavor.

Pediococcus acidilactici FZU106 alleviates high-fat diet-induced lipid metabolism disorder in association with the modulation of intestinal microbiota in hyperlipidemic rats.

Probiotics have been proved to have beneficial effects in improving hyperlipidemia. The purpose of the current research was to investigate the ameliorative effects of Pediococcus acidilactici FZU106, isolated from the traditional brewing of Hongqu rice wine, on lipid metabolism and intestinal microbiota in high-fat diet (HFD)-induced hyperlipidemic rats. Results showed that P. acidilactici FZU106 intervention obviously inhibited the abnormal increase of body weight, ameliorated serum and liver biochemical parameters related to lipid metabolism and oxidative stress. Histopathological evaluation also showed that P. acidilactici FZU106 could significantly reduce the excessive lipid accumulation in liver caused by HFD-feeding. Furthermore, P. acidilactici FZU106 intervention significantly increased the short-chain fatty acids (SCFAs) levels in HFD-fed rats, which was closely related to the changes of intestinal microbial composition and metabolism. Intestinal microbiota profiling by high-throughput sequencing demonstrated that P. acidilactici FZU106 intervention evidently increased the proportion of Butyricicoccus, Pediococcus, Rothia, Globicatella and [Eubacterium]_coprostanoligenes_group, and decreased the proportion of Corynebacterium_1, Psychrobacter, Oscillospira, Facklamia, Pseudogracilibacillus, Clostridium_innocuum_group, Enteractinococcus and Erysipelothrix in HFD-fed rats. Additionally, P. acidilactici FZU106 significantly regulated the mRNA levels of liver genes (including CD36, CYP7A1, SREBP-1c, BSEP, LDLr and HMGCR) involved in lipid metabolism and bile acid homeostasis. Therefore, these findings support the possibility that P. acidilactici FZU106 has the potential to reduce the disturbance of lipid metabolism by regulating intestinal microflora and liver gene expression profiles.

Ganoderic acid A from Ganoderma lucidum protects against alcoholic liver injury through ameliorating the lipid metabolism and modulating the intestinal microbial composition.

Alcoholic liver injury is mainly caused by long-term excessive alcohol consumption and has become a global public threat to human health. It is well known that Ganoderma lucidum has excellent beneficial effects on liver function and lipid metabolism. The object of this study was to investigate the hepatoprotective effects of ganoderic acid A (GAA, one of the main triterpenoids in G. lucidum) against alcohol-induced liver injury and reveal the underlying mechanisms of its protective effects. The results showed that oral administration of GAA significantly inhibited the abnormal elevation of the liver index, serum total triglyceride (TG), cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in mice exposed to alcohol intake, and also significantly protected the liver against alcohol-induced excessive lipid accumulation and pathological changes. Besides, alcohol-induced oxidative stress in the liver was significantly ameliorated by the dietary intervention of GAA through decreasing the hepatic levels of lactate dehydrogenase (LDH) and malondialdehyde (MDA), and increasing hepatic activities of catalase (CAT), superoxide dismutase (SOD), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and hepatic levels of glutathione (GSH). In addition, GAA intervention evidently ameliorated intestinal microbial disorder by markedly increasing the abundance of Muribaculaceae, Prevotellaceae, Jeotgalicoccus, Bilophila, Family_XIII_UCG_001, Aerococcus, Ruminococcaceae_UCG_005, Harryflintia, Christensenellaceae, Rumonpcpccaceae, Prevotelaceae_UCG_001, Clostridiales_vadinBB60_group, Parasutterella and Bifidobacterium, but decreasing the proportion of Lactobacillus, Burkholderia_Caballeroria_Paraburkholderia, Escherichia_Shigella and Erysipelatoclostridium. Furthermore, liver metabolomics based on UPLC-QTOF/MS demonstrated that oral administration of GAA had a significant regulatory effect on the composition of liver metabolites in mice exposed to alcohol intake, especially the levels of the biomarkers involved in the metabolic pathways of riboflavin metabolism, glycine, serine and threonine metabolism, pyruvate metabolism, glycolysis/gluconeogenesis, biosynthesis of unsaturated fatty acids, synthesis and degradation of ketone bodies, fructose and mannose metabolism. Moreover, dietary supplementation of GAA significantly regulated the hepatic mRNA levels of lipid metabolism and inflammatory response related genes. Conclusively, these findings demonstrate that GAA has beneficial effects on alleviating alcohol-induced liver injury and is expected to become a new functional food ingredient for the prevention of alcoholic liver injury.

Corrigendum to "Ganoderic acids-rich ethanol extract from Ganoderma lucidum protects against alcoholic liver injury and modulates intestinal microbiota in mice with excessive alcohol intake" [Curr. Res. Food Sci. 5(2022) 515-530].

[This corrects the article DOI: 10.1016/j.crfs.2022.02.013.].

Organic chromium derived from the chelation of Ganoderma lucidum polysaccharide and chromium (III) alleviates metabolic syndromes and intestinal microbiota dysbiosis induced by high-fat and high-fructose diet.

Organic chromium is of great interest and has become an important chromium supplement resource in recent years because of its low toxicity and easy absorption. In our previous study, we synthesized a novel organic chromium [GLP-Cr] through the chelation of Ganoderma lucidum polysaccharide and chromium (III). The purpose of this study was to investigate the beneficial effects of GLP-Cr on the improvement of metabolic syndromes (MetS) in mice fed with a high-fat and high-fructose diet (HFHFD) and its mechanism of action. The results indicated that oral administration of GLP-Cr inhibited the excessive exaltation of body weight, glucose tolerance, fasting blood glucose and lipid levels, hepatic total cholesterol (TC), triglyceride (TG) levels caused by HFHFD. Besides, 16S rRNA amplicon sequencing showed that GLP-Cr intervention evidently ameliorated intestinal microbiota dysbiosis by changing the proportions of some intestinal microbial phylotypes. In addition, correlation network-based analysis indicated that the key intestinal microbial phylotypes were closely related to biochemical parameters associated with MetS under GLP-Cr intervention. Liver metabolomics analysis suggested that GLP-Cr intervention significantly regulated the levels of some biomarkers involved in alpha-linolenic acid metabolism, fatty acid biosynthesis, steroid hormone biosynthesis, glycerophospholipid metabolism, glycerolipid metabolism, steroid hormone biosynthesis, primary bile acid biosynthesis, and so on. Moreover, GLP-Cr intervention regulated liver mRNA levels of key genes associated with glucose and lipid metabolism. The mRNA level of glucose transporter type 4 (Glut4) was markedly increased by GLP-Cr intervention, and the mRNA levels of phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6Pase) in the liver were significantly decreased. Meanwhile, GLP-Cr intervention significantly decreased hepatic mRNA levels of cluster of differentiation 36 (Cd36), acetyl-CoA carboxylase 1 (Acc1) and sterol regulatory element binding protein-1c (Srebp-1c), indicating that GLP-Cr intervention inhibited the excessive accumulation of free fatty acids in the liver. These findings suggest that the prevention of hyperglycemia and dyslipidemia by GLP-Cr may be closely related to the regulation of gut microbial composition and hepatic metabolic pathways, thus GLP-Cr can be serving as a functional component in the prevention of MetS.

The Protective Effects of Ganoderic Acids from Ganoderma lucidum Fruiting Body on Alcoholic Liver Injury and Intestinal Microflora Disturbance in Mice with Excessive Alcohol Intake.

This study aimed to investigate the protective effects of ganoderic acids (GA) from Ganoderma lucidum against liver injury and intestinal microbial disorder in mice with excessive alcohol intake. Results showed GA supplement significantly inhibited the abnormal elevation of the liver index, serum lipid parameters, aspartate aminotransferase and alanine aminotransferase in mice exposed to alcohol intake, and also significantly protected the excessive lipid accumulation and pathological changes. Alcohol-induced oxidative stress in the liver was significantly ameliorated by GA intervention through reducing the levels of maleic dialdehyde and lactate dehydrogenase and increasing the levels of glutathione, catalase, superoxide dismutase and alcohol dehydrogenase. Intestinal microbiota profiling demonstrated GA intervention modulated the composition of intestinal microflora by increasing the levels of Lactobacillus, Faecalibaculum, Romboutsia, Bifidobacterium and decreasing the Helicobacter level. Furthermore, liver metabolomic profiling suggested GA intervention had a remarkable regulatory effect on liver metabolism with excessive alcohol consumption. Moreover, GA intervention regulated mRNA levels of alcohol metabolism, fatty lipid metabolism, oxidative stress, bile acid biosynthesis and metabolism-related genes in the liver. Conclusively, these findings demonstrate GA intervention can significantly relieve alcoholic liver injury and it is hopeful to become a new functional food ingredient for the prevention of alcoholic liver injury.