Construction of a Synthetic Microbial Community for Enzymatic Pretreatment of Wheat Straw for Biogas Production via Anaerobic Digestion.

Biological pretreatment is a viable method for enhancing biogas production from straw crops, with the improvement in lignocellulose degradation efficiency being a crucial factor in this process. Herein, a metagenomic approach was used to screen core microorganisms (Bacillus subtilis, Acinetobacter johnsonii, Trichoderma viride, and Aspergillus niger) possessing lignocellulose-degrading abilities among samples from three environments: pile retting wheat straw (WS), WS returned to soil, and forest soil. Subsequently, synthetic microbial communities were constructed for fermentation-enzyme production. The crude enzyme solution obtained was used to pretreat WS and was compared with two commercial enzymes. The synthetic microbial community enzyme-producing pretreatment (SMCEP) yielded the highest enzymatic digestion efficacy for WS, yielding cellulose, hemicellulose, and lignin degradation rates of 39.85, 36.99, and 19.21%, respectively. Furthermore, pretreatment of WS with an enzyme solution, followed by anaerobic digestion achieved satisfactory results. SMCEP displayed the highest cumulative biogas production at 801.16 mL/g TS, which was 38.79% higher than that observed for WS, 22.15% higher than that of solid-state commercial enzyme pretreatment and 25.41% higher than that of liquid commercial enzyme pretreatment. These results indicate that enzyme-pretreated WS can significantly enhance biogas production. This study represents a solution to the environmental burden and energy use of crop residues.

Association between predicted fat mass, predicted lean mass, predicted percent fat and type 2 diabetes mellitus in Japanese adults: a retrospective study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is known to have obesity as a risk factor. Body mass index cannot distinguish between lean mass and fat mass. We aimed to examine the association between predicted fat mass, predicted lean mass, predicted percent fat and risk of T2DM in Japanese adults. We also explored whether these three new parameters could predict T2DM better than other obesity markers. METHODS: This present study is a secondary data analysis. The study enrolled 20,944 Japanese individuals who participated in the NAGALA medical assessment program between 2004 and 2015. 15,453 participants who are eligible and have complete information were included to our analysis. Through the use of Kaplan-Meier curve, restricted cubic spline and univariate and multivariate Cox regression analysis, the relationship between predicted fat mass, predicted lean mass, predicted percent fat and T2DM risk was examined. The area under the curve method was used to assess the differences between these markers of obesity. RESULTS: A total of 373 cases of T2DM occurred over a median time of 5.4 years. In the male group, we found a U-shaped connection between predicted fat mass, predicted lean mass, and T2DM onset (p value, non-linearity < 0.05). A linear relationship was found between predicted percent fat and T2DM onset. The linear relationship was also found in the female group for predicted fat mass, and predicted percent fat. And for women, predicted lean mass was not an independent predictor. The area under the curve (AUC) for predicted fat mass, predicted lean mass, predicted percent fat in men was 0.673 (95%CI: 0.639 ~ 0.707), 0.598 (95%CI: 0.561 ~ 0.635), 0.715 (95%CI: 0.684 ~ 0.745), respectively. In males, WHtR was the strongest predictor (AUC 0.7151, 95%CI: 0.684 ~ 0.746), followed by predicted percent fat (AUC 0.7150, 95%CI: 0.684 ~ 0.745). In the females, WHtR was also the strongest predictor (AUC 0.758, 95%CI: 0.703 ~ 0.813), followed by body mass index (AUC 0.757, 95%CI: 0.704 ~ 0.811) and predicted percent fat (AUC 0.742, 95%CI: 0.687 ~ 0.798). CONCLUSION: Predicted fat mass, predicted lean mass, predicted percent fat were strongly connected with an increased risk for developing T2DM in Japanese, particularly in males. WHtR and predicted percent fat had a slightly better discrimination than other common obesity indicators in males. In the females, predicted fat mass and predicted percent fat were associated with T2DM risk, WHtR and body mass index had the slightly higher predictive power.

Acute Tai Chi Chuan exercise enhances sustained attention and elicits increased cuneus/precuneus activation in young adults.

BACKGROUND: The potential for acute exercise to enhance attention has been discussed in the literature. However, the neural mechanisms by which acute exercise affects attention remain elusive. METHOD: In this study, we first identified an optimized acute Tai Chi Chuan (ATCC) exercise protocol that enhances sustained attention performance and then aimed to determine the neural substrates of exercise-enhanced attention. Reaction time (RT) from the psychomotor vigilance test (PVT) was used to evaluate sustained attention. In Experiment 1, improvements in RTs were compared among six different exercise protocols. In Experiment 2, the participants completed the PVT in an MRI scanner on both rest and exercise days. RESULTS: Experiment 1 showed that practicing TCC 3 times for a total of 20 minutes, followed by 10-minute rest periods, resulted in the largest improvements in RTs. Experiment 2 showed that ATCC enhanced sustained attention, as evidenced by shorter RTs, and resulted in greater cuneus/precuneus activation after exercise than in the rest condition. Exercise-induced changes in brain activities across a distributed network exhibited significant correlations with attention. CONCLUSION: Therefore, this study indicates that ATCC effectively enhances sustained attention and underscores the key role of the cuneus/precuneus and frontoparietal-cerebellar regions in facilitating vigilance among young adults.

Combined CNN and RNN Neural Networks for GPR Detection of Railway Subgrade Diseases.

Vehicle-mounted ground-penetrating radar (GPR) has been used to non-destructively inspect and evaluate railway subgrade conditions. However, existing GPR data processing and interpretation methods mostly rely on time-consuming manual interpretation, and limited studies have applied machine learning methods. GPR data are complex, high-dimensional, and redundant, in particular with non-negligible noises, for which traditional machine learning methods are not effective when applied to GPR data processing and interpretation. To solve this problem, deep learning is more suitable to process large amounts of training data, as well as to perform better data interpretation. In this study, we proposed a novel deep learning method to process GPR data, the CRNN network, which combines convolutional neural networks (CNN) and recurrent neural networks (RNN). The CNN processes raw GPR waveform data from signal channels, and the RNN processes features from multiple channels. The results show that the CRNN network achieves a higher precision at 83.4%, with a recall of 77.3%. Compared to the traditional machine learning method, the CRNN is 5.2 times faster and has a smaller size of 2.6 MB (traditional machine learning method: 104.0 MB). Our research output has demonstrated that the developed deep learning method improves the efficiency and accuracy of railway subgrade condition evaluation.

Purification, Structural Analysis and Cardio-Protective Activity of Polysaccharides from Radix Astragali.

Two polysaccharides, named APS2-I and APS3-I, were purified from the water extract of Radix Astragali. The average molecular weight of APS2-I was 1.96 × 106 Da and composed of Man, Rha, GlcA, GalA, Glc, Gal, Xyl, and Ara in a molar ratio of 2.3:4.8:1.7:14.0:5.8:11.7:2.8:12.6, while the average molecular weight of APS3-I was 3.91 × 106 Da and composed of Rha, GalA, Glc, Gal, and Ara in a molar ratio of 0.8:2.3:0.8:2.3:4.1. Biological evaluation showed APS2-I and APS3-I had significant antioxidant activity and myocardial protection activity. Furthermore, total polysaccharide treatment could significantly enhance hemodynamic parameters and improve cardiac function in rat ischemia and reperfusion isolated heart models. These results provided important information for the clinical application of APS in the field of cardiovascular disease and implied that Astragalus polysaccharides (APS) could be considered as a reference for the quality control of Radix Astragali.

Paired Derivatization Approach with H/D-Labeled Hydroxylamine Reagents for Sensitive and Accurate Analysis of Monosaccharides by Liquid Chromatography Tandem Mass Spectrometry.

Monosaccharides play important roles in biological processes. Sensitive and accurate analyses of monosaccharides remain challenging because of their high hydrophilicities and poor ionization efficiencies. Here, we developed a paired derivatization approach with H/D-labeled hydroxylamines for simultaneous quantification of 12 monosaccharides by liquid chromatography tandem mass spectrometry (LC-MS/MS). O-(4-Methoxybenzyl)hydroxylamine hydrochloride (4-MOBHA·HCl) showed higher derivatization efficiency for monosaccharides compared to six other hydroxylamine analogues. The derivatization of monosaccharides was readily achieved in an aqueous solution. Furthermore, the deuterium-labeled isotope reagent, d3-4-MOBHA·HCl, was newly synthesized to stably label monosaccharides to improve its accuracy and precision in complex matrix analysis. As a result, 12 monosaccharides were rapidly detected by LC-MS/MS within 16 min with significant improvements in chromatographic separation and retention time. The detection sensitivity increased by 83 to 1600-fold with limits of quantitation ranging from 0.25 to 3.00 fmol. With the paired derivatization strategy, the monosaccharides could be accurately quantified with good linearity (R2 > 0.99) and satisfactory accuracy (recoveries: 85-110%). Using this method, we achieved sensitive and accurate quantification of the monosaccharide composition of herbal polysaccharides and the change in monosaccharide levels in human cell lines under physiopathological conditions. More importantly, the developed method was able to differentiate between the levels of the monosaccharides in fecal samples of human ulcerative colitis (UC) patients and UC mice compared to their respective controls. The differential monosaccharides determined in human feces provided a good diagnostic performance in distinguishing the UC patients from healthy individuals, showing potential for clinical application.

Changes in white matter functional networks during wakefulness and sleep.

Blood oxygenation level-dependent (BOLD) signals in the white matter (WM) have been demonstrated to encode neural activities by showing structure-specific temporal correlations during resting-state and task-specific imaging of fiber pathways with various degrees of correlations in strength and time delay. Previous neuroimaging studies have shown state-dependent functional connectivity and regional amplitude of signal fluctuations in brain gray matter across wakefulness and nonrapid eye movement (NREM) sleep cycles. However, the functional characteristics of WM during sleep remain unknown. Using simultaneous electroencephalography and functional magnetic resonance imaging data during wakefulness and NREM sleep collected from 66 healthy participants, we constructed 10 stable WM functional networks using clustering analysis. Functional connectivity between these WM functional networks and regional amplitude of WM signal fluctuations across multiple low-frequency bands were evaluated. In general, decreased WM functional connectivity between superficial and middle layer WM functional networks was observed from wakefulness to sleep. In addition, functional connectivity between the deep and cerebellar networks was higher during light sleep and lower during both wakefulness and deep sleep. The regional fluctuation amplitude was always higher during light sleep and lower during deep sleep. Importantly, slow-wave activity during deep sleep negatively correlated with functional connectivity between WM functional networks but positively correlated with fluctuation strength in the WM. These observations provide direct physiological evidence that neural activities in the WM are modulated by the sleep-wake cycle. This study provided the initial mapping of functional changes in WM during sleep.

Heparin-free after 3000 IU heparin loaded in veno-venous ECMO supported acute respiratory failure patients with hemorrhage risk: a novel anti-coagulation strategy.

BACKGROUND: The anti-coagulation protocol of patients with hemorrhage risk primary disease who need extracorporeal membrane oxygenation (ECMO) supported is controversial. This study evaluated the feasibility of a new anti-coagulation strategy, that is heparin-free after 3000 IU heparin loaded in veno-venous ECMO (VV ECMO) supported acute respiratory failure patients with hemorrhage risk. METHODS: A retrospective study was performed in a series of hemorrhage risk patients supported with VV ECMO at the First Affiliated Hospital of Zhengzhou University, between June 2012 to Sept 2020. A total of 70 patients received a low heparin bolus of 3000 units for cannulation but without subsequent, ongoing heparin administration. Patients were divided into survival (n = 25) and non-survival group (n = 45). Data of coagulation, hemolysis and membrane lung function were calculated and analyzed. The complications of patients were recorded. Finally, the binary Logistic regression was conducted. RESULTS: The longest heparin-free time was 216 h, and the mean heparin-free time was 102 h. Compared with survivors, the non-survivors were showed higher baseline SOFA score and lower platelet counts in 0.5 h, 24 h, 48 h and 96 h after ECMO applied. However, there was no significant differences between survivors and non-survivors in ACT, APTT, INR, D-dimer, fibrinogen, LDH, blood flow rate, Δp and Ppost-MLO2 (all p < 0.05) of all different time point. Moreover, only the baseline SOFA score was significantly associated with mortality (p < 0.001, OR(95%CI): 2.754 (1.486-5.103)) while the baseline levels of ACT, APTT, INR, platelet, D-dimer, fibrinogen and LDH have no association with mortality. The percentage of thrombosis complications was 54.3% (38/70) including 3 oxygenator changed but there was no significant difference of complications in survival and non-survival groups (p > 0.05). CONCLUSIONS: The anticoagulation protocol that no heparin after a 3000 units heparin bolus in VV ECMO supported acute respiratory failure patients with hemorrhage risk is feasible.

State-of-the-Art Review of Ground Penetrating Radar (GPR) Applications for Railway Ballast Inspection.

In the past 20 years, many studies have been performed on ballast layer inspection and condition evaluation with ground penetrating radar (GPR). GPR is a non-destructive means that can reflect the ballast layer condition (fouling, moisture) by analysing the received signal variation. Even though GPR detection/inspection for ballast layers has become mature, some challenges still need to be stressed and solved, e.g., GPR indicator (for reflecting fouling level) development, quantitative evaluation for ballast fouling levels under diverse field conditions, rapid GPR inspection, and combining analysis of GPR results with other data (e.g., track stiffness, rail acceleration, etc.). Therefore, this paper summarised earlier studies on GPR application for ballast layer condition evaluation. How the GPR was used in the earlier studies was classified and discussed. In addition, how to correlate GPR results with ballast fouling level was also examined. Based on the summary, future developments can be seen, which is helpful for supplementing standards of ballast layer evaluation and maintenance.

Genomic Epidemiology, Evolution, and Transmission Dynamics of Porcine Deltacoronavirus.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown once again that coronavirus (CoV) in animals are potential sources for epidemics in humans. Porcine deltacoronavirus (PDCoV) is an emerging enteropathogen of swine with a worldwide distribution. Here, we implemented and described an approach to analyze the epidemiology of PDCoV following its emergence in the pig population. We performed an integrated analysis of full genome sequence data from 21 newly sequenced viruses, along with comprehensive epidemiological surveillance data collected globally over the last 15 years. We found four distinct phylogenetic lineages of PDCoV, which differ in their geographic circulation patterns. Interestingly, we identified more frequent intra- and interlineage recombination and higher virus genetic diversity in the Chinese lineages compared with the USA lineage where pigs are raised in different farming systems and ecological environments. Most recombination breakpoints are located in the ORF1ab gene rather than in genes encoding structural proteins. We also identified five amino acids under positive selection in the spike protein suggesting a role for adaptive evolution. According to structural mapping, three positively selected sites are located in the N-terminal domain of the S1 subunit, which is the most likely involved in binding to a carbohydrate receptor, whereas the other two are located in or near the fusion peptide of the S2 subunit and thus might affect membrane fusion. Finally, our phylogeographic investigations highlighted notable South-North transmission as well as frequent long-distance dispersal events in China that could implicate human-mediated transmission. Our findings provide new insights into the evolution and dispersal of PDCoV that contribute to our understanding of the critical factors involved in CoVs emergence.

Coordinated changes of gut microbiome and lipidome differentiates nonalcoholic steatohepatitis (NASH) from isolated steatosis.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease encompasses isolated steatosis or nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH). NASH develops from isolated steatosis with obscure driving forces. We aim to identify key factors promoting this transition. METHODS: Following 21-week of high-fat diet feeding, obese mice were classified into two groups termed as isolated steatosis and NASH based on hematoxylin-eosin staining of liver histology. The integrated multi-omics analysis of lipidome, transcriptome and gut microbiome were performed in mice with isolated steatosis and NASH, and confirmed in human samples. RESULTS: Livers in mice with NASH lost most lipids, and the transcriptional landscape was also changed dramatically in mice with NASH in relative to mice with isolated steatosis. Plasma lipidome analysis demonstrated a very clear difference between these two groups of mice, which was partially recapitulated in serum of patients with isolated steatosis and NASH. The microbiota composition revealed that Bacteroides genus and Bacteroides uniformis species decreased while Mucispirillum genus and Mucispirillum schaedleri species increased largely in mice with NASH. More importantly, we found that Bacteroides uniformis correlated positively with triglycerides (TGs) and negatively with free fatty acids (FFAs) and PE(18:1/20:4), while Mucispirillum schaedleri correlated positively with FFAs, LysoPC(20:3), LysoPC(20:4) and DG(16:1/18:2). Mechanically, administration of Bacteroides uniformis increased specific TGs, and decreased hepatic injury and inflammation in diet-induced mice. CONCLUSIONS: Overall, through multi-omics integration, we identified a microbiota-lipid axis promoting the initiation of NASH from isolated steatosis, which might provide a novel perspective on NASH pathogenesis and treatment.

Incidence and outcomes of acute respiratory distress syndrome in intensive care units of mainland China: a multicentre prospective longitudinal study.

OBJECTIVES: To evaluate the incidence and mortality of acute respiratory distress syndrome (ARDS) in medical/respiratory intensive care units (MICUs/RICUs) to assess ventilation management and the use of adjunct therapy in routine clinical practice for patients fulfilling the Berlin definition of ARDS in mainland China. METHODS: This was a multicentre prospective longitudinal study. Patients who met the Berlin definition of ARDS were included. Baseline data and data on ventilator management and the use of adjunct therapy were collected. RESULTS: Of the 18,793 patients admitted to participating ICUs during the study timeframe, 672 patients fulfilled the Berlin ARDS criteria and 527 patients were included in the analysis. The most common predisposing factor for ARDS in 402 (77.0) patients was pneumonia. The prevalence rates were 9.7% (51/527) for mild ARDS, 47.4% (250/527) for moderate ARDS, and 42.9% (226/527) for severe ARDS. In total, 400 (75.9%) patients were managed with invasive mechanical ventilation during their ICU stays. All ARDS patients received a tidal volume of 6.8 (5.8-7.9) mL/kg of their predicted body weight and a positive end-expository pressure (PEEP) of 8 (6-12) cmH2O. Recruitment manoeuvres (RMs) and prone positioning were used in 61 (15.3%) and 85 (16.1%) ventilated patients, respectively. Life-sustaining care was withdrawn from 92 (17.5%) patients. When these patients were included in the mortality analysis, 244 (46.3%) ARDS patients (16 (31.4%) with mild ARDS, 101 (40.4%) with moderate ARDS, and 127 (56.2%) with severe ARDS) died in the hospital. CONCLUSIONS: Among the 18 ICUs in mainland China, the incidence of ARDS was low. The rates of mortality and withdrawal of life-sustaining care were high. The recommended lung protective strategy was followed with a high degree of compliance, but the implementation of adjunct treatment was lacking. These findings indicate the potential for improvement in the management of patients with ARDS in China. TRIAL REGISTRATION: Clinicaltrials.gov NCT02975908 . Registered on 29 November 2016-retrospectively registered.

WZ66, a novel acetyl-CoA carboxylase inhibitor, alleviates nonalcoholic steatohepatitis (NASH) in mice.

The global prevalence of nonalcoholic steatohepatitis (NASH) increases incredibly. NASH ends up to advanced liver disease, which is highly threatening to human health. Currently, treatment of NASH is very limited. Acetyl-CoA carboxylases (ACC1/ACC2) are proved as effective drug targets for NASH. We aimed to develop novel ACC inhibitors and evaluate their therapeutic value for NASH prevention. ACC inhibitors were obtained through structure-based drug design, synthesized, screened from ACC enzymatic measurement platform and elucidated in cell culture-based assays and animal models. The lipidome and microbiome analysis were integrated to assess the effects of WZ66 on lipids profiles in liver and plasma as well as gut microbiota in the intestine. WZ66 was identified as a novel ACC1/2 inhibitor. It entered systemic circulation rapidly and could accumulate in liver. WZ66 alleviated NASH-related liver features including steatosis, Kupffer cells and hepatic stellate cells activation in diet-induced obese mice. The triglycerides (TGs) and other lipids including diglycerides (DGs), phosphatidylcholine (PC) and sphingomyelin (SM) were decreased in WZ66-treated mice as evidenced by lipidome analysis in livers. The lipids profiles in plasma were also altered with WZ66 treatment. Plasma TG were moderately increased, while the activation of SREBP1c was not detected. WZ66 also downregulated the abundance of Allobaculum, Mucispirillum and Prevotella genera as well as Mucispirillum schaedleri species in gut microbiota. WZ66 is an ideal lead compound and a potential drug candidate deserving further investigation in the therapeutics of NASH.

Human intestinal microbiota derived metabolism signature from a North American native botanical Oplopanax horridus with UPLC/Q-TOF-MS analysis.

Oplopanax horridus, widely distributed in North America, is an herbal medicine traditionally used by Pacific indigenous peoples for various medical conditions. After oral ingestion, constituents in O. horridus extract (OhE) could be converted to their metabolites by the enteric microbiome before absorption. In this study, in order to mimic gut environment, the OhE was biotransformed using the enteric microbiome of healthy human subjects. For accurate and reliable data collection with optimized approaches in sample preparation and analytical conditions, ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry were used to characterize parent constituents and their metabolites. In the extract, 20 parent compounds were identified including polyynes, sesquiterpenes, monoterpeondids, phenylpropanoids and phenolic acids. After the biotransformation, a total of 78 metabolites were identified, of which 37 belonged to polyynes metabolites. The common biotransformation pathways are hydroxylation, acetylization, methylation and demethylation. Based on the pathway distributions, the metabolism signature of OhE has been explored. The metabolism pathways of OhE compounds are dependent on their structural classifications and hydrophilic/hydrophobic properties. In summary, with comprehensive analysis, we systematically investigated human microbiome-derived OhE metabolites. The enteric microbial metabolism signature provides novel information for future effective use of O. horridus.

Interspecies Transmission, Genetic Diversity, and Evolutionary Dynamics of Pseudorabies Virus.

BACKGROUND: Pseudorabies virus (PRV) causes Aujeszky's disease in pigs and can be transmitted to other mammals, including humans. In the current study, we systematically studied the interspecies transmission and evolutionary history of PRV. METHODS: We performed comprehensive analysis on the phylodynamics, selection, and structural biology to summarize the phylogenetic and adaptive evolution of PRV based on all available full-length and major glycoprotein sequences. RESULTS: PRV can be divided into 2 main clades with frequent interclade and intraclade recombination. Clade 2.2 (variant PRV) is currently the most prevalent genotype worldwide, and most commonly involved in cross-species transmission events (including humans). We also found that the population size of clade 2.2 has increased since 2011, and the effective reproduction number was >1 from 2011 to 2016, indicating that PRV may be still circulating in swine herds and is still a risk in relation with cross-species transmission in China. Of note, we identified amino acid sites in some important glycoproteins gB, gC, gD, and gE that may be associated with PRV adaptation to new hosts and immune escape to vaccines. CONCLUSIONS: Our study provides important genetic insight into the interspecies transmission and evolution of PRV within and between different hosts that warrant additional surveillance.

Functional Metabolomics Characterizes a Key Role for N-Acetylneuraminic Acid in Coronary Artery Diseases.

BACKGROUND: As new biomarkers of coronary artery diseases (CAD) emerge via metabolomics, the underlying functional mechanisms remain to be elucidated. Functional metabolomics aims to translate metabolomics-derived biomarkers to disease mechanisms. METHODS: A cohort of 2324 patients who underwent coronary angiography from 4 independent centers was studied. A combination of ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry in the negative ion mode was used for untargeted analysis of metabolites in plasma. Significant differential metabolites were identified by cross-comparisons with and within CAD types, including normal coronary artery, nonobstructvie coronary atherosclerosis, stable angina, unstable angina, and acute myocardial infarction. A tandem liquid chromatography-mass spectrometry-based approach using isotope-labeled standard addition was subsequently performed for targeted analysis of the metabolic marker N-acetylneuraminic acid (Neu5Ac). A functional metabolomics strategy was proposed to investigate the role of Neu5Ac in the progression of CAD by using in vitro and in vivo models. RESULTS: We identified a total of 36 differential metabolites, 35 of which were confirmed with reference compounds. Elevation of Neu5Ac was observed in plasma during CAD progression in center 1 (P=4.0e-64, n=2019) and replicated in 3 independent centers (n=305). The increased level of Neu5Ac in plasma was confirmed by accurate targeted quantification. Mechanistically, Neu5Ac was able to trigger myocardial injury in vitro and in vivo by activation of the Rho/Rho-associated coiled-coil containing protein kinase signaling pathway through binding to RhoA and Cdc42, but not Rac1. Silencing neuraminidase-1, the enzyme that regulates Neu5Ac generation, ameliorated oxygen-glucose deprivation-induced injury in cardiomyocytes and ligation/isoprenaline-induced myocardial ischemia injury in rats. Pharmacological inhibition of neuraminidase by anti-influenza drugs, oseltamivir and zanamivir, also protected cardiomyocytes and the heart from myocardial injury. CONCLUSIONS: Functional metabolomics identified a key role for Neu5Ac in acute myocardial infarction, and targeting neuraminidase-1 may represent an unrecognized therapeutic intervention for CAD.

Serum-plasma matched metabolomics for comprehensive characterization of benign thyroid nodule and papillary thyroid carcinoma.

Metabolomics offers a noninvasive methodology to identify metabolic markers for pathogenesis and diagnosis of diseases. This work aimed to characterize circulating metabolic signatures of benign thyroid nodule (BTN) and papillary thyroid carcinoma (PTC) via serum-plasma matched metabolomics. A cohort of 1,540 serum-plasma matched samples and 114 tissues were obtained from healthy volunteers, BTN and PTC patients enrolled from 6 independent centers. Untargeted metabolomics was determined by liquid chromatography-quadrupole time-of-flight mass spectrometric and multivariate statistical analyses. The use of serum-plasma matched samples afforded a broad-scope detection of 1,570 metabolic features. Metabolic phenotypes revealed significant pattern differences for healthy versus BTN and healthy versus PTC. Perturbed metabolic pathways related mainly to amino acid and lipid metabolism. It is worth noting that, BTN and PTC showed no significant differences but rather overlap in circulating metabolic signatures, and this observation was replicated in all study centers. For differential diagnosis of healthy versus thyroid nodules (BTN + PTC), a panel of 6 metabolic markers, namely myo-inositol, α-N-phenylacetyl-L-glutamine, proline betaine, L-glutamic acid, LysoPC(18:0) and LysoPC(18:1) provided area under the curve of 97.68% in the discovery phase and predictive accuracies of 84.78-98.18% in the 4 validation centers. Taken together, serum-plasma matched metabolomics showed significant differences in circulating metabolites for healthy versus nodules but not for BTN versus PTC. Our results highlight the true metabolic nature of thyroid nodules, and potentially decrease overtreatment that exposes patients to unnecessary risks.

Construction of Synthetic Microbiota for Reproducible Flavor Compound Metabolism in Chinese Light-Aroma-Type Liquor Produced by Solid-State Fermentation.

Natural microbiota plays an essential role in flavor compounds used in traditional food fermentation; however, the fluctuation in natural microbiota results in inconsistency in food quality. Thus, it is critical to reveal the core microbiota for flavor compound production and to construct a synthetic core microbiota for use in constant food fermentation. Here, we reveal the core microbiota based on their flavor production and cooccurrence performance, using Chinese light-aroma-type liquor as a model system. Five genera, Lactobacillus, Saccharomyces, Pichia, Geotrichum, and Candida, were identified to be the core microbiota. The synthetic core microbiota of these five genera presented a reproducible dynamic profile similar to that in the natural microbiota. A Monte Carlo test showed that the effects of five environmental factors (lactic acid, ethanol, and acetic acid contents, moisture, and pH) on the synthetic microbiota distribution were highly significant (P < 0.01), similar to those effects on a natural fermentation system. In addition, 77.27% of the flavor compounds produced by the synthetic core microbiota showed a similar dynamic profile (ρ > 0) with that in the natural liquor fermentation process, and the flavor profile presented a similar composition. It indicated that the synthetic core microbiota is efficient for reproducible flavor metabolism. This work established a method for identifying core microbiota and constructing a synthetic microbiota for reproducible flavor compounds. This work is of great significance for the tractable and constant production of various fermented foods.IMPORTANCE The transformation from natural fermentation to synthetic fermentation is essential in constructing a constant food fermentation process, which is the premise for stably making high-quality food. According to flavor-producing and cooccurring functions in dominant microbes, we provided a system-level approach to identify the core microbiota in Chinese light-aroma-type liquor fermentation. In addition, we successfully constructed a synthetic core microbiota to simulate the microbial community succession and flavor compound production in the in vitro system. The constructed synthetic core microbiota could not only facilitate a mechanistic understanding of the structure and function of the microbiota but also be beneficial for constructing a tractable and reproducible food fermentation process.

Host-range shift of H3N8 canine influenza virus: a phylodynamic analysis of its origin and adaptation from equine to canine host.

Prior to the emergence of H3N8 canine influenza virus (CIV) and the latest avian-origin H3N2 CIV, there was no evidence of a circulating canine-specific influenza virus. Molecular and epidemiological evidence suggest that H3N8 CIV emerged from H3N8 equine influenza virus (EIV). This host-range shift of EIV from equine to canine hosts and its subsequent establishment as an enzootic CIV is unique because this host-range shift was from one mammalian host to another. To further understand this host-range shift, we conducted a comprehensive phylodynamic analysis using all the available whole-genome sequences of H3N8 CIV. We found that (1) the emergence of H3N8 CIV from H3N8 EIV occurred in approximately 2002; (2) this interspecies transmission was by a reassortant virus of the circulating Florida-1 clade H3N8 EIV; (3) once in the canine species, H3N8 CIV spread efficiently and remained an enzootic virus; (4) H3N8 CIV evolved and diverged into multiple clades or sublineages, with intra and inter-lineage reassortment. Our results provide a framework to understand the molecular basis of host-range shifts of influenza viruses and that dogs are potential "mixing vessels" for the establishment of novel influenza viruses.

Chitosan Oligosaccharide Ameliorates Nonalcoholic Fatty Liver Disease (NAFLD) in Diet-Induced Obese Mice.

Nonalcoholic fatty liver disease (NAFLD) is a global epidemic, and there is no standard and efficient therapy for it. Chitosan oligosaccharide (COS) is widely known to have various biological effects, and in this study we aimed to evaluate the liver-protective effect in diet-induced obese mice for an enzymatically digested product of COS called COS23 which is mainly composed of dimers and trimers. An integrated analysis of the lipidome and gut microbiome were performed to assess the effects of COS23 on lipids in plasma and the liver as well as on intestinal microbiota. Our results revealed that COS23 obviously attenuated hepatic steatosis and ameliorated liver injury in diet-induced obese mice. The hepatic toxic lipids-especially triglycerides (TGs) and free fatty acids (FFAs)-were decreased dramatically after COS23 treatment. COS23 regulated lipid-related pathways, especially inhibiting the expressions of FFA-synthesis-related genes and inflammation-related genes. Furthermore, COS23 could alter lipid profiles in plasma. More importantly, COS23 also decreased the abundance of Mucispirillum and increased the abundance of Coprococcus in gut microbiota and protected the intestinal barrier by up-regulating the expression of tight-junction-related genes. In conclusion, COS23, an enzymatically digested product of COS, might serve as a promising candidate in the clinical treatment of NAFLD.