Enhancing Acid Resistance of Aspergillus niger Pectin Lyase through Surface Charge Design for Improved Application in Juice Clarification.

Pectin lyases (PNLs) can enhance juice clarity and flavor by degrading pectin in highly esterified fruits, but their inadequate acid resistance leads to rapid activity loss in juice. This study aimed to improve the acid resistance of Aspergillus niger PNL pelA through surface charge design. A modification platform was established by fusing pelA with a protein tag and expressing the fusion enzyme in Escherichia coli. Four single-point mutants were identified to increase the surface charge using computational tools. Moreover, the combined mutant M6 (S514D/S538E) exhibited 99.8% residual activity at pH 3.0. The M6 gene was then integrated into the A. niger genome using a multigene integration system to obtain the recombinant PNL AM6. Notably, AM6 improved the light transmittance of orange juice to 45.3%, which was 8.39 times higher than that of pelA. In conclusion, AM6 demonstrated the best-reported acid resistance, making it a promising candidate for industrial juice clarification.

Simultaneous quantitative LC-MS/MS analysis of 13 apolipoproteins and lipoprotein (a) in human plasma.

Numerous studies have revealed a close correlation between the levels of apolipoproteins (Apos) (including lipoprotein(a) [Lp(a)]) and an increased risk of cardiovascular disease in recent decades. However, clinically, lipid profiling remains limited to the conventional plasma levels of cholesterol, triglyceride, ApoA1, and ApoB, which brings the necessity to quantify more apolipoproteins in human plasma. In this study, we simultaneously quantified 13 apolipoproteins and Lp(a) in 5 µL of human plasma using the LC-MS/MS platform. A method was developed for the precise detection of Lp(a), ApoA1, A2, A5, B, C1, C2, C3, D, E, H, L1, M, and J. Suitable peptides were selected and optimized to achieve clear separation of each peak. Method validation consisting of linearity, sensitivity, accuracy and precision, recovery, and matrix effects was evaluated. The intra-day CV ranged from 0.58% to 14.2% and the inter-day CV ranged from 0.51% to 13.3%. The recovery rates ranged from 89.8% to 113.7%, while matrix effects ranged from 85.4% to 113.9% for all apolipoproteins and Lp(a). Stability tests demonstrated that these apolipoproteins remained stable for 3 days at 4 °C and 7 days at -20 °C. This validated method was successfully applied to human plasma samples obtained from 45 volunteers. The quantitative results of ApoA1, ApoB, and Lp(a) exhibited a close correlation with the results from the immunity transmission turbidity assay. Collectively, we developed a robust assay that can be used for high-throughput quantification of apolipoproteins and Lp(a) simultaneously for investigating related risk factors in patients with dyslipidemia.

Gut microbiota-dependent phenylacetylglutamine in cardiovascular disease: current knowledge and new insights.

Phenylacetylglutamine (PAGln) is an amino acid derivate that comes from the amino acid phenylalanine. There are increasing studies showing that the level of PAGln is associated with the risk of different cardiovascular diseases. In this review, we discussed the metabolic pathway of PAGln production and the quantitative measurement methods of PAGln. We summarized the epidemiological evidence to show the role of PAGln in diagnostic and prognostic value in several cardiovascular diseases, such as heart failure, coronary heart disease/atherosclerosis, and cardiac arrhythmia. The underlying mechanism of PAGln is now considered to be related to the thrombotic potential of platelets via adrenergic receptors. Besides, other possible mechanisms such as inflammatory response and oxidative stress could also be induced by PAGln. Moreover, since PAGln is produced across different organs including the intestine, liver, and kidney, the cross-talk among multiple organs focused on the function of this uremic toxic metabolite. Finally, the prognostic value of PAGln compared to the classical biomarker was discussed and we also highlighted important gaps in knowledge and areas requiring future investigation of PAGln in cardiovascular diseases.

Prediction of the risk of 3-year chronic kidney disease among elderly people: a community-based cohort study.

OBJECTIVE: We conducted a community-based cohort study to predict the 3-year occurrence of chronic kidney disease (CKD) among population aged ≥60 years. METHOD: Participants were selected from two communities through randomized cluster sampling in Jiading District of Shanghai, China. The two communities were randomly divided into a development cohort (n = 12012) and a validation cohort (n = 6248) with a 3-year follow-up. Logistic regression analysis was used to determine the independent predictors. A nomogram was established to predict the occurrence of CKD within 3 years. The area under the curve (AUC), the calibration curve and decision curve analysis (DCA) curve were used to evaluate the model. RESULT: At baseline, participants in development cohort and validation cohort were with the mean age of 68.24 ± 5.87 and 67.68 ± 5.26 years old, respectively. During 3 years, 1516 (12.6%) and 544 (8.9%) new cases developed CKD in the development and validation cohorts, respectively. Nine variables (age, systolic blood pressure, body mass index, exercise, previous hypertension, triglycerides, fasting plasma glucose, glycated hemoglobin and serum creatinine) were included in the prediction model. The AUC value was 0.742 [95% confidence interval (CI), 0.728-0.756] in the development cohort and 0.881(95%CI, 0.867-0.895) in the validation cohort, respectively. The calibration curves and DCA curves demonstrate an effective predictive model. CONCLUSION: Our nomogram model is a simple, reasonable and reliable tool for predicting the risk of 3-year CKD in community-dwelling elderly people, which is helpful for timely intervention and reducing the incidence of CKD.

Phylogenetic analysis of endogenous viral elements in the rice genome reveals local chromosomal evolution in Oryza AA-genome species.

Introduction: Rice genomes contain endogenous viral elements homologous to rice tungro bacilliform virus (RTBV) from the pararetrovirus family Caulimoviridae. These viral elements, known as endogenous RTBV-like sequences (eRTBVLs), comprise five subfamilies, eRTBVL-A, -B, -C, -D, and -X. Four subfamilies (A, B, C, and X) are present to a limited degree in the genomes of the Asian cultivated rice Oryza sativa (spp. japonica and indica) and the closely related wild species Oryza rufipogon. Methods: The eRTBVL-D sequences are widely distributed within these and other Oryza AA-genome species. Fifteen eRTBVL-D segments identified in the japonica (Nipponbare) genome occur mostly at orthologous chromosomal positions in other AA-genome species. The eRTBVL-D sequences were inserted into the genomes just before speciation of the AA-genome species. Results and discussion: Ten eRTBVL-D segments are located at six loci, which were used for our evolutionary analyses during the speciation of the AA-genome species. The degree of genetic differentiation varied among the eRTBVL-D segments. Of the six loci, three showed phylogenetic trees consistent with the standard speciation pattern (SSP) of the AA-genome species (Type A), and the other three represented phylogenies different from the SSP (Type B). The atypical phylogenetic trees for the Type B loci revealed chromosome region-specific evolution among the AA-genome species that is associated with phylogenetic incongruences: complex genome rearrangements between eRTBVL-D segments, an introgression between the distant species, and low genetic diversity of a shared eRTBVL-D segment. Using eRTBVL-D as an indicator, this study revealed the phylogenetic incongruence of local chromosomal regions with different topologies that developed during speciation.

Wheat milling across history altered sugar bioaccessibility assessed using TIM-1 in vitro digestion model.

The differences in wheat flour characteristics caused by ancient (pestle and mortar), old (stone hand mill), and modern (roller and cyclone) milling techniques and their effect on in vitro starch digestibility of wheat porridge using the simulated TIM Gastrointestinal Model (TIM-1) were investigated. Ancient flour (AF) was the coarsest flour (∼70 % is >1000 µm), followed by old wholemeal flour (OWF) and old refined flour (ORF) with similar particle size distribution showing one prominent peak (at ∼1000 µm for OWF and ∼800 µm for ORF). Modern refined flour (MRF) had a monomodal distribution centered at a particle size of ∼100 µm, while modern wholemeal flour (MWF) particle size was distributed between 40 and 600 µm. MRF and MWF porridges had higher cumulative sugar bioaccessibility than OWF and AF porridges, with ORF porridge having an intermediate cumulative sugar bioaccessibility. Characterizing the cumulative sugar bioaccessibility profile with a shifted logistic model allows identifying that the maximum sugar bioaccessibility and rate of sugar release were significantly higher (p < 0.05) for MRF and MWF compared to OWF and AF porridges, while the induction times were shorter, demonstrating the importance of processing on modulating starch digestibility.

A multi-center cross-sectional study on identification of influencing factors of medical students' emotional engagement in China.

BACKGROUND: Studies exploring influencing factors of emotional engagement among medical students are scarce. Thus, we aimed to identify influencing factors of medical students' emotional engagement. METHODS: We carried out a multi-center cross-sectional study among 10,901 medical students from 11 universities in China. The Chinese version of Utrecht Work Engagement Scale-Student version (UWES-S) was used to evaluate emotional engagement level of medical students. The predictors related to engagement level were determined by the logistic regression analysis. Furthermore, we constructed a nomogram to predict emotional engagement level of medical students. RESULTS: A total of 10,576 sample were included in this study. The mean emotional engagement score was 74.61(± 16.21). In the multivariate logistic regression model, we found that males showed higher engagement level compared with females [odds ratio (OR) (95% confidence interval (CI)): 1.263 (1.147, 1.392), P < 0.001]. Medical students from the second batches of medical universities had higher engagement level and from "Project 985" universities had lower engagement level compared with 211 project universities [OR (95%CI): 1.376 (1.093, 1.733), P = 0.007; OR (95%CI): 0.682 (0.535, 0.868), P = 0.002]. Medical students in grade 4 and grade 2 presented lower engagement level compared with in grade 1 [OR (95%CI): 0.860 (0.752, 0.983), P = 0.027; OR (95%CI): 0.861 (0.757, 0.980), P = 0.023]. Medical students lived in provincial capital cities had higher engagement level compared with in country [OR (95%CI): 1.176 (1.022, 1.354), P = 0.024]. Compared with eight-year emotional duration, medical students in other emotional duration (three-year and four-year) had lower engagement level [OR (95%CI): 0.762 (0.628, 0.924), P = 0.006]. Medical students' engagement level increased with increases of grade point average and interest in studying medicine. Medical students learned by converging style showed lower engagement level [OR (95%CI): 0.827 (0.722, 0.946), P = 0.006] compared with accommodating style. The model showed good discriminative ability (area under curve = 0.778), calibrating ability and clinical utility. CONCLUSIONS: We identified influencing factors of medical students' emotional engagement and developed a nomogram to predict medical students' emotional engagement level, providing reference and convenience for educators to assess and improve emotional engagement level of medical students. It is crucial for educators to pay more attention to emotional engagement of medical students and adopt effective strategies to improve their engagement level.

Synthesis of piperidines and pyridine from furfural over a surface single-atom alloy Ru1CoNP catalyst.

The sustainable production of value-added N-heterocycles from available biomass allows to reduce the reliance on fossil resources and creates possibilities for economically and ecologically improved synthesis of fine and bulk chemicals. Herein, we present a unique Ru1CoNP/HAP surface single-atom alloy (SSAA) catalyst, which enables a new type of transformation from the bio-based platform chemical furfural to give N-heterocyclic piperidine. In the presence of NH3 and H2, the desired product is formed under mild conditions with a yield up to 93%. Kinetic studies show that the formation of piperidine proceeds via a series of reaction steps. Initially, in this cascade process, furfural amination to furfurylamine takes place, followed by hydrogenation to tetrahydrofurfurylamine (THFAM) and then ring rearrangement to piperidine. DFT calculations suggest that the Ru1CoNP SSAA structure facilitates the direct ring opening of THFAM resulting in 5-amino-1-pentanol which is quickly converted to piperidine. The value of the presented catalytic strategy is highlighted by the synthesis of an actual drug, alkylated piperidines, and pyridine.

Identification of molecular signatures in acute myocardial infarction based on integrative analysis of proteomics and transcriptomics.

BACKGROUND: Myocardial infarction (MI) is one of the most serious cardiovascular diseases, characterized by a rapid and irreversible decline in myocardial function. Early detection of patients with MI and prolonging the optimal therapeutic window of acute myocardial infarction (AMI) are particularly important. This study aimed to identify the diagnostic biomarkers and novel therapeutic targets for acute myocardial infarction. METHOD: We generated the AMI mouse models by ligating the proximal left anterior descending coronary artery. Six time points-Sham, AMI 10-min, 1-h, 6-h, 24-h, and 72-h-were chosen to examine the molecular changes that occur during the AMI process. RNA-seq and DIA-MS were performed on the infarcted left ventricular tissues of AMI mice at each time point. Co-expression pattern genes were screened from myocardial infarction samples at different time points by time-series analysis. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to examine these genes. Using the Interactive Gene/Protein Retrieval Tool (STRING) database, the protein-protein interaction network (PPI) was constructed and the hub genes were identified. In order to evaluate the diagnostic value of hub genes, a receiver operating characteristic (ROC) curve was constructed. An independent data set, GSE163772, confirmed the diagnostic value of hub genes further. RESULT: We obtained the expression profiles at different time points after the occurrence of heart failure through high-throughput sequencing, and found 167 genes with similar expression patterns through time series analysis. The immune response and immune-related pathways had the greatest enrichment of these genes. Among them, Itgb2 Syk, Tlr4, Tlr2, Itgax, and Lcp2 may play key roles as hub genes. Combined with the results of proteomic analysis, it was found that the expression of Coro1a in both omics increased with time. The results of external validation showed that TLR2, ITGAX, and LCP2 had good predictive ability for AMI diagnosis. CONCLUSION: Itgb2, Syk, Tlr4, Tlr2, Itgax, Lcp2 and Coro1a are considered to be the seven key genes significantly associated with AMI. Our results may provide potential targets for the prevention of adverse ventricular remodeling and the treatment of AMI.

Increased circulating phenylacetylglutamine concentration elevates the predictive value of cardiovascular event risk in heart failure patients.

BACKGROUND: Phenylacetylglutamine (PAGln)-a newly discovered microbial metabolite produced by phenylalanine metabolism-is reportedly associated with cardiovascular events via adrenergic receptors. Nonetheless, its association with cardiovascular outcomes in heart failure (HF) patients remains unknown. OBJECTIVES: This study aimed to prospectively investigate the prognostic value of PAGln for HF. METHODS: Plasma PAGln levels were quantified by liquid chromatography-tandem mass spectrometry. We first assessed the association between plasma PAGln levels and the incidence of adverse cardiovascular events in 3152 HF patients (including HF with preserved and reduced ejection fraction) over a median follow-up period of 2 years. The primary endpoint was the composite of cardiovascular death or heart transplantation. We then assessed the prognostic role of PAGln in addition to the classic biomarker N-terminal pro-B-type natriuretic peptide (NT-proBNP). The correlation between PAGln levels and ß-blocker use was also investigated. RESULTS: In total, 520 cardiovascular deaths or heart transplantations occurred in the HF cohort. Elevated PAGln levels were independently associated with a higher risk of the primary endpoint in a dose-response manner, regardless of HF subtype. Concurrent assessment of PAGln and NT-proBNP levels enhanced risk stratification among HF patients. PAGln further showed prognostic value at low NT-proBNP levels. Additionally, the interaction effects between PAGln and ß-blocker use were not significant. CONCLUSIONS: Plasma PAGln levels are an independent predictor of an increased risk of adverse cardiovascular events in HF. Our work could provide joint and complementary prognostic value to NT-proBNP levels in HF patients.

The digestive fate of beef versus plant-based burgers from bolus to stool.

Ultra-processed, plant-based burgers (PB) and traditional comminuted-beef burgers (BB) share similar organoleptic characteristics, yet a knowledge gap exists in understanding how consumption of these divergent physical structures alters the lipemic response and gut microbiota. PB, comprised of highly refined ingredients, is formulated with no intact whole food structure, while BB entraps lipids throughout the myofibrillar protein network. PB presented significantly higher free fatty acid (FFA) bioaccessibility (28.2 ± 4.80 %) compared to BB (8.73 ± 0.52 %), as obtained from their FFA release profiles over digestion time after characterizing them with a modified logistic model (SLM), using the simulated TIM Gastro-Intestinal Model (TIM-1). Additionally, the rate of lipolysis, k, obtained from the SLM for PB (90% CI [0.0175, 0.0277] min-1) was higher than for BB (90% CI [0.0113, 0.0171] min-1). Using the Simulated Human Intestinal Microbial Ecosystem (SHIME®), the Firmicutes to Bacteroidetes ratio (F/B ratio) was significantly higher for PB than BB; and linear discriminant analysis effect size (LEfSe) showed Clostridium and Citrobacter were more highly represented in the microbial community for the PB feed, whereas BB feed differentially enriched Megasphaera, Bacteroides, Alistipes, and Blautia at the genus level. Additionally, short-chain fatty acid (SCFA) production was altered (p < 0.05) site-specifically in each colon vessel, which could be attributed to the available substrates and changes in microbial composition. Total SCFAs were significantly higher for PB in the ascending colon (AC) and descending colon (DC) but higher for BB only in the transverse colon (TC). This research illustrates the crucial role of meat analog physical structure in modulating nutritional aspects beyond food composition alone.

Effect of anxiety and depression on self-reported adverse reactions to COVID-19 vaccine: a cross-sectional study in Shanghai, China.

BACKGROUND: The association of anxiety and depression with adverse reactions after receipt of coronavirus disease 2019 (COVID-19) vaccine is not clear among the general population. This study aims to evaluate the effect of anxiety and depression on self-reported adverse reactions to COVID-19 vaccine. METHODS: The cross-sectional study was conducted during April-July 2021. Participants completing the two doses of vaccine were included in this study. Sociodemographic information, anxiety and depression levels and adverse reactions after the first dose of vaccine for all participants were collected. The anxiety and depression levels were assessed by the Seven-item Generalized Anxiety Disorder Scale and the Nine-item Patient Health Questionnaire Scale, respectively. The multivariate logistic regression analysis was used to examine the association between anxiety and depression and adverse reactions. RESULTS: A total of 2161 participants were enrolled in this study. The prevalence of anxiety and depression was 13% (95% confidence interval (CI), 11.3-14.2%) and 15% (95%CI, 13.6-16.7%), respectively. Of the 2161 participants, 1607 (74%; 95% CI, 73-76%) reported at least one adverse reaction after the first dose of the vaccine. Pain at the injection site (55%) and fatigue and headache (53% and 18%, respectively) were the most commonly reported local and systemic adverse reactions, respectively. Participants with anxiety or depression or both were more likely to report local and systemic adverse reactions (P < 0.05). CONCLUSION: The results suggest that anxiety and depression increase the risk of self-reported adverse reactions to COVID-19 vaccine. Consequently, appropriate psychological interventions before vaccination will help to reduce or alleviate symptoms of vaccination.

Association between cardiopulmonary function, health-related quality of life and cognitive impairment among the older nursing home residents in Shanghai, China.

BACKGROUND: This study aimed to examine the association between cardiopulmonary function, health-related quality of life (HRQOL) and cognitive function among nursing home residents aged 80 years and over. METHODS: A nursing home-based, cross-sectional study was implemented among 677 aged over 80 years in Shanghai, China. A total of 197 participants underwent effective cardiopulmonary function examinations. Mini-Mental Status Examination (MMSE) and Short Form-36 scales (SF-36) were used to assess cognitive function and HRQOL, respectively. RESULTS: Decline in left ventricular ejection fractions (LVEF) [adjusted odds ratio (AOR), 1.98; 95% confidential interval (CI), 1.03-3.81)] and vital capacity (VC) (AOR, 2.08; 95%CI, 1.07-4.04) was associated with cognitive impairment. After adjusting confounding factors, relationships between cognitive function and physical functioning (PF) (AOR, 0.98; 95%CI, 0.97-0.99) still existed. CONCLUSIONS: Healthcare professionals should pay more attention to cardiopulmonary health and HRQOL in the nursing home residents. Actions of public health strategies focus on the improvement of cardiopulmonary function, and PF among older nursing home residents with cognitive impairment is required.

Palm Lipid Emulsion Droplet Crystallinity and Gastric Acid Stability in Relation to in vitro Bioaccessibility and in vivo Gastric Emptying.

It is poorly understood how the physical state of emulsified triacylglycerol (TAG) alters colloidal behavior in the gastrointestinal tract to modulate lipid digestion and absorption. We, therefore, aimed to investigate the individual and combined effects on fatty acid (FA) bioaccessibility using the dynamic TIM-1 in vitro digestion model and integrate the results with those from a human clinical study. Four 20% oil-in-water emulsions with overlapping particle size distributions contained either partially crystalline solid (palm stearin) or liquid (palm olein) lipid droplets at 37°C and either the colloidally acid-stable Tween 80 (2.2%) or acid-unstable Span 60 (2.5%) emulsifier. Experimental meals were fed to the TIM-1, and jejunal and ileal dialysates were analyzed over 6 h to measure free FA concentration. Cumulative FA bioaccessibility was significantly higher for the liquid stable emulsion compared to all others (p < 0.05), which did not differ (p > 0.05). Emulsified TAG physical state was associated with differences in overall bioaccessibility (higher for liquid state TAG) in the colloidally stable emulsions, but this difference was blunted in droplets susceptible to acidic flocculation. In contrast, human postprandial TAG concentrations did not differ significantly between the emulsions. The discrepancy may relate to differences in in vivo gastric emptying (GE) as evidenced by ultrasonography. When the in vivo differences in GE were accounted for in follow-up TIM-1 experiments, the findings aligned more closely. Cumulative FA bioaccessibility for the liquid stable emulsion no longer differed significantly from the other emulsions, and SU's bioaccessibility was the lowest, consistent with the in vivo observations. This work highlights the potential for TAG physical state and colloidal stability to interactively alter behavior in the gastrointestinal tract with implications for FA absorption, and the importance of establishing and improving in vitro-in vivo correlations in food-nutrition research.

The Association Between Statin Use and Risk of Chronic Kidney Disease in Community-Dwelling Older People in Shanghai, China.

Purpose: The effects of statins on renal outcomes have already been studied in patients with chronic kidney disease (CKD); however, data on the general population are limited. We evaluated the association between statin use and risk of CKD in community-dwelling older people in Shanghai, China. Patients and Methods: This registry-based cohort study was conducted in four communities in four districts in Shanghai. Participants with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 in 2016 were eligible for the study, and new-onset CKD in 2017, 2018, and 2019 was recorded. Poisson generalized linear models were conducted to examine the relationships among statin therapy, dyslipidemia, and CKD; linear mixed-effects models were conducted to examine the relationships between statin therapy and changes in eGFR. All analyses were performed with both conventional adjustment and propensity score-matching methods. Results: Of the study cohort of 2455 participants (41.1% men; average age, 68.06 years), 624 (25.4%) were treated with stains. Two propensity score-matched cohorts of 604 participants each were analyzed (statin users and nonusers). Statin use was significantly associated with a decreased risk of new-onset CKD with hazard ratios (HRs) and 95% confidence intervals (CIs) of 0.73 (0.59 to 0.91) (p<0.01) in the unmatched cohort and 0.75 (0.59 to 0.97) (p=0.02) in the matched cohort. There were significant differences in the eGFR decline between statin users and nonusers from baseline to 3 years in the unmatched and matched cohorts (both p<0.05). In addition, both statin users and nonusers with dyslipidemia experienced more new-onset CKD (both p<0.05). Conclusion: Statin use was significantly associated with a decreased risk of new-onset CKD and a slower decline in eGFR in community-dwelling older people. Meanwhile, dyslipidemia was a risk factor for CKD progression among both statin users and nonusers.

Nomograms for Predicting Medical Students' Perceptions of the Learning Environment: Multicenter Evidence From Medical Schools in China.

Medical students' perceptions of the medical school learning environment (MSLE) have an important impact on their professional development, and physical and mental health. Few studies reported potential factors that influenced medical students' perceptions of MSLE. Thus, the main goal of this study was to identify influencing factors for medical students' perception levels of MSLE. The perception levels of MSLE were assessed by the Johns Hopkins Learning Environment Scale. The univariate and multivariate logistic regression analyses were performed to identify significant predictors for the perceptions of MSLE. The nomograms were established to predict medical students' perception levels of MSLE. In the multivariate logistic regression model, gender, university category, grade, mother education level, learning environment of schools, interests in medicine, and Kolb learning experience were significantly associated with medical students' perceptions of MSLE. Correspondently, the nomograms were built based on significant variables identified by the univariate logistic regression analysis. The validation of the nomograms showed that the model had promising predictive accuracy, discrimination, and accordance (area under the curve (AUC) = 0.751). This study identified influencing factors of medical students' perceptions of MSLE. It is essential to implement corresponding interventions to improve medical students' perceptions.

Construction of Bone Metastasis-Specific Regulation Network Based on Prognostic Stemness-Related Signatures in Prostate Cancer.

Background: We planned to uncover the cancer stemness-related genes (SRGs) in prostate cancer (PCa) and its underlying mechanism in PCa metastasis. Methods: We acquired the RNA-seq data of 406 patients with PCa from the TCGA database. Based on the mRNA stemness index (mRNAsi) calculated by one-class logistic regression (OCLR) algorithm, SRGs in PCa were extracted by WGCNA. Univariate and multivariate regression analyses were applied to uncover OS-associated SRGs. Gene Set Variation Analysis (GSVA), Gene Set Enrichment Analysis (GSEA), and Pearson's correlation analysis were performed to discover the possible mechanism of PCa metastasis. The significantly correlated transcription factors of OS-associated SRGs were also identified by Pearson's correlation analysis. ChIP-seq was applied to validate the binding relationship of TFs and OS-associated SRGs and spatial transcriptome and single-cell sequencing were performed to uncover the location of key biomarkers expression. Lastly, we explored the specific inhibitors for SRGs using CMap algorithm. Results: We identified 538 differentially expressed genes (DEGs) between non-metastatic and metastatic PCa. Furthermore, OS-associated SRGs were identified. The Pearson correlation analysis revealed that FOXM1 was significantly correlated with NEIL3 (correlation efficient =0.89, p < 0.001) and identified hallmark_E2F_targets as the potential pathway mechanism of NEIL3 promoting PCa metastasis (correlation efficient =0.58, p < 0.001). Single-cell sequencing results indicated that FOXM1 regulating NEIL3 may get involved in the antiandrogen resistance of PCa. Rottlerin was discovered to be a potential target drug for PCa. Conclusion: We constructed a regulatory network based on SRGs associated with PCa metastasis and explored possible mechanism.

Integrated RNA- and miRNA-sequencing analysis identifies molecular basis for stress-induced heart injury in mouse models.

BACKGROUND: Work stress and its contribution to cardiovascular diseases are well documented in recent years, but its molecular mechanisms are still not clear. In this study, we aimed to explore the potential pathophysiological mechanisms of stress-induced heart injury in mouse models. METHODS: The RNA- and miRNA- sequencing profiles from five stress-treated mice and five control mice were performed. After normalization, differentially expressed genes (DEGs) and miRNAs (DEmiRs) were identified using the edgeR method. Then, based on the functional enrichment analysis and protein-protein interaction (PPI) network, as well as miRNA-mRNA interactome, the core DEGs and DEmiRs associated with stress-induced heart injury were marked and validated by qPCR, and the DEmiR targets were validated in vitro. RESULTS: A total of 293 genes and 29 miRNAs were identified as DEGs and DEmiRs respectively, and Alb, Stat1, C3, Irf7, Usp18 were hub genes in the PPI network. The enrichment pathways were related to inflammation and immune, coagulation, oxidative phosphorylation, vascular development, cell cycle and extracellular matrix (ECM), which likely mediated the biological injury processes or reflected the results of damage. The target DEGs of DEmiRs were clustered in angiogenesis, immune system process and ECM. After the validation in vitro, we found that miR-29b-3p mimics could down-regulate the expression of its predicted targets, Pxdn and Col15a1. CONCLUSIONS: The findings revealed a molecular basis from the gene and miRNA level for the heart injury associated with stress. miR-29b-3p, as a potential target to repair stress-induced ECM disorder in heart, deserves further study.

Effect of fucoidan on ethanol-induced liver injury and steatosis in mice and the underlying mechanism.

BACKGROUND: Alcoholic liver disease is caused as a result of chronic alcohol consumption. In this study, we used an alcoholic liver injury mouse model to investigate the effect of fucoidan on ethanol-induced liver injury and steatosis and the underlying mechanisms. METHODS: All mice were randomly divided into four groups: 1) control group, 2) model group, 3) diammonium glycyrrhizinate treatment group (200 mg/kg body weight), and 4) fucoidan treatment group (300 mg/kg body weight). Administration of ethanol for 8 weeks induced liver injury and steatosis in mice. RESULTS: Fucoidan treatment decreased serum alanine aminotransferase activity, serum total cholesterol levels, and hepatic triglyceride levels, and improved the morphology of hepatic cells. Fucoidan treatment upregulated the expression of AMPKα1, SIRT1, and PGC-1α and inhibited the expression of ChREBP and HNF-1α. The levels of hepatic IL-6 and IL-18 were significantly decreased in the fucoidan group. Further, the levels of cytochrome P450-2E1 (CYP2E1), glucose-regulated protein (GRP) 78, and 3-nitrotyrosine (3-NT) in hepatic tissues were reduced in the fucoidan group as compared to the model group. Fucoidan significantly reversed the reduction of ileac Farnesoid X receptor (FXR) and fibroblast growth factor 15 (FGF15) levels induced by alcohol-feeding and reduced CYP7A1 (cholesterol 7α-hydroxylase) expression and total bile acid levels in the liver tissue. In addition, fucoidan regulated the structure of gut flora, with increased abundance of Prevotella and decreased abundance of Paraprevotella and Romboutsia as detected by 16S rDNA high-throughput sequencing. CONCLUSION: Fucoidan inhibited alcohol-induced steatosis and disorders of bile acid metabolism in mice through the AMPKα1/SIRT1 pathway and the gut microbiota-bile acid-liver axis and protected against alcohol-induced liver injury in vivo.

Effect of nicotinamide riboside on lipid metabolism and gut microflora-bile acid axis in alcohol-exposed mice.

Alcoholic liver disease (ALD) is the most common complication of alcohol abuse, while we lack safe and effective treatment for ALD. This study aimed to explore the effects of nicotinamide riboside (NR) on lipid metabolism and gut microflora-bile acid axis in alcohol-exposed mice. NR significantly improved liver histopathological damage and abnormal liver function. NR as a provider of nicotinamide adenine dinucleotide (NAD+) increased the NAD+/NADH ratio. Meanwhile, NR inhibited the activation of the protein phosphatase 1 signaling pathway, decreased the liver triglyceride and total bile acid levels, and reduced lipid accumulation. According to the results of gut microflora species analysis, NR intervention changed the microbial community structure at the phylum, family and genus levels, and the species abundances returned to a level similar to these of the normal control group. Besides, the results of high-performance liquid chromatograph-mass spectrometry showed that NR intervention resulted in fecal bile acid levels tending to be normal with decreased chenodeoxycholic acid level and increased deoxycholic acid and hyocholic acid levels. Spearman's correlation analysis showed a correlation between gut microflora and bile acids. Therefore, NR supplementation has the potential to prevent ALD, and its mechanism may be related to regulating lipid metabolism disorders and the gut microflora-bile acid axis.