Effects of Inhibitors on the Transcriptional Profiling of Gluconobater oxydans NL71 Genes after Biooxidation of Xylose into Xylonate

D-Xylonic acid belongs to the top 30 biomass-based platform chemicals and represents a promising application of xylose. Until today, Gluconobacter oxydans NL71 is the most efficient microbe capable of fermenting xylose into xylonate. However, its growth is seriously inhibited when concentrated lignocellulosic hydrolysates are used as substrates due to the presence of various degraded compounds formed during biomass pretreatment. Three critical lignocellulosic inhibitors were thereby identified, i.e., formic acid, furfural, and 4-hydroxybenzaldehyde. As microbe fermentation is mostly regulated at the genome level, four groups of cell transcriptomes were obtained for a comparative investigation by RNA sequencing of a control sample with samples treated separately with the above-mentioned inhibitors. The digital gene expression profiles screened 572, 714 genes, and 408 DEGs was obtained by the comparisons among four transcriptomes. A number of genes related to the different functional groups showed characteristic expression patterns induced by three inhibitors, in which 19 genes were further tested and confirmed by qRT-PCR. We extrapolated many differentially expressed genes that could explain the cellular responses to the inhibitory effects. We provide results that enable the scientific community to better define the molecular processes involved in the microbes' responses to lignocellulosic inhibitors during the cellular biooxidation of xylose into xylonic acid

HYDRA: Hypergradient Data Relevance Analysis for Interpreting Deep Neural Networks

The behaviors of deep neural networks (DNNs) are notoriously resistant to human interpretations. In this paper, we propose Hypergradient Data Relevance Analysis, or HYDRA, which interprets the predictions made by DNNs as effects of their training data. Existing approaches generally estimate data contributions around the final model parameters and ignore how the training data shape the optimization trajectory. By unrolling the hypergradient of test loss w.r.t. the weights of training data, HYDRA assesses the contribution of training data toward test data points throughout the training trajectory. In order to accelerate computation, we remove the Hessian from the calculation and prove that, under moderate conditions, the approximation error is bounded. Corroborating this theoretical claim, empirical results indicate the error is indeed small. In addition, we quantitatively demonstrate that HYDRA outperforms influence functions in accurately estimating data contribution and detecting noisy data labels. The source code is available at https://github.com/cyyever/aaai_hydra_8686

Effects of domestic cooking process on the chemical and biological properties of dietary phytochemicals

peer-reviewedFoods are good sources of vitamins, minerals and dietary fibers as well as phytochemicals, which are beneficial for the human body as nutritional supplements. The nutritional value (crude fibers, crude proteins, crude fats, flavonols, carotenoids, polyphenols, glucosinolate, chlorophyll, and ascorbic acid) and biological or functional properties (antioxidant activity, anticancer activity, or anti-mutagenic activity) of foods can be well retained and protected with the appropriate cooking methods. The chemical, physical and enzyme modifications that occur during cooking will alter the dietary phytochemical antioxidant capacity and digestibility. This paper reviewed the recent advances on the effects of domestic cooking process on the chemical and biological properties of dietary phytochemicals. Furthermore, the possible mechanisms underlying these changes were discussed, and additional implications and future research goals were suggested. The domestic cooking process for improving the palatability of foods and increasing the bioavailability of nutrients and bioactive phytochemicals has been well supported

Translocation and metabolism of tricresyl phosphate in rice and microbiome system: Isomer-specific processes and overlooked metabolites.

Tricresyl phosphate (TCP) is extensively used organophosphorus flame retardants and plasticizers that posed risks to organisms and human beings. In this study, the translocation and biotransformation behavior of isomers tri-p-cresyl phosphate (TpCP), tri-m-cresyl phosphate (TmCP), and tri-o-cresyl phosphate (ToCP) in rice and rhizosphere microbiome was explored by hydroponic exposure. TpCP and TmCP were found more liable to be translocated acropetally, compared with ToCP, although they have same molecular weight and similar Kow. Rhizosphere microbiome named microbial consortium GY could reduce the uptake of TpCP, TmCP, and ToCP in rice tissues, and promote rice growth. New metabolites were successfully identified in rice and microbiome, including hydrolysis, hydroxylated, methylated, demethylated, methoxylated, and glucuronide- products. The methylation, demethylation, methoxylation, and glycosylation pathways of TCP isomers were observed for the first time in organisms. What is more important is that the demethylation of TCPs could be an important and overlooked source of triphenyl phosphate (TPHP), which broke the traditional understanding of the only man- made source of toxic TPHP in the environment. Active members of the microbial consortium GY during degradation were revealed and metagenomic analysis indicated that most of active populations contained TCP- degrading genes. It is noteworthy that the strains and function genes in microbial consortium GY that responsible for TCP isomers’ transformation were different. These results can improve our understanding of the translocation and transformation of organic pollutant isomers in plants and rhizosphere microbiome

Áttekintés a műfajkutatás tendenciáiról és lehetőségeiről. Útban egy kognitív szemléletű műfajelmélet felé

<p>Delta, theta, alpha and beta band power at different locations during the walking test (μV²).</p

FABP4-mediated lipid droplet formation in Streptococcus uberis-infected macrophages supports host defence

Foamy macrophages containing prominent cytoplasmic lipid droplets (LDs) are found in a variety of infectious diseases. However, their role in Streptococcus uberis-induced mastitis is unknown. Herein, we report that S. uberis infection enhances the fatty acid synthesis pathway in macrophages, resulting in a sharp increase in LD levels, accompanied by a significantly enhanced inflammatory response. This process is mediated by the involvement of fatty acid binding protein 4 (FABP4), a subtype of the fatty acid-binding protein family that plays critical roles in metabolism and inflammation. In addition, FABP4 siRNA inhibitor cell models showed that the deposition of LDs decreased, and the mRNA expression of Tnf, Il1b and Il6 was significantly downregulated after gene silencing. As a result, the bacterial load in macrophages increased. Taken together, these data demonstrate that macrophage LD formation is a host-driven component of the immune response to S. uberis. FABP4 contributes to promoting inflammation via LDs, which should be considered a new target for drug development to treat infections

Efficacy and safety of a combination of miglitol, metformin and insulin aspart in the treatment of type 2 diabetes

Purpose: To study the clinical effect of combining insulin aspart with different drugs in the treatment oftype 2 diabetes mellitus (T2DM).Methods: Two hundred and thirty-seven T2DM patients admitted to the Endocrinology Department of the Second Affiliated Hospital of Kunming Medical University from March to September 2018 were selected as subjects in this study. Miglitol and metformin were used in combination with insulin aspart in the treatment of T2DM. In addition, data on the effectiveness and safety of different treatment options,such as patient’s weight, waist circumference, blood glucose indicators, indices of heart, liver and kidney functions, and incidence of complications were recorded and compared between the two groups.Results: The use of a combination of miglitol and insulin aspart produced an excellent hypoglycaemic effect, and it significantly reduced the incidence of sensory neuropathy in the eyes and distal limbs (p &lt; 0.05). The use of combination of metformin and insulin aspart effectively protected the heart and kidney, and prevented hypoglycaemia (p &lt; 0.05).Conclusion: These results suggest that treatment with a combination of miglitol and insulin aspart is suitable for patients with T2DM whose blood sugar levels are out of control, while combined treatment with metformin and insulin aspart is more suited for patients who desire to reduce blood sugar and blood lipids through weight loss, and patients with cardiac and renal insufficiency

Taurine reprograms mammary-gland metabolism and alleviates inflammation induced by Streptococcus uberis in mice

Streptococcus uberis (S. uberis) is an important pathogen causing mastitis, which causes continuous inflammation and dysfunction of mammary glands and leads to enormous economic losses. Most research on infection continues to be microbial metabolism-centric, and many overlook the fact that pathogens require energy from host. Mouse is a common animal model for studying bovine mastitis. In this perspective, we uncover metabolic reprogramming during host immune responses is associated with infection-driven inflammation, particularly when caused by intracellular bacteria. Taurine, a metabolic regulator, has been shown to effectively ameliorate metabolic diseases. We evaluated the role of taurine in the metabolic regulation of S. uberis-induced mastitis. Metabolic profiling indicates that S. uberis exposure triggers inflammation and metabolic dysfunction of mammary glands and mammary epithelial cells (the main functional cells in mammary glands). Challenge with S. uberis upregulates glycolysis and oxidative phosphorylation in MECs. Pretreatment with taurine restores metabolic homeostasis, reverses metabolic dysfunction by decrease of lipid, amino acid and especially energy disturbance in the infectious context, and alleviates excessive inflammatory responses. These outcomes depend on taurine-mediated activation of the AMPK–mTOR pathway, which inhibits the over activation of inflammatory responses and alleviates cellular damage. Thus, metabolic homeostasis is essential for reducing inflammation. Metabolic modulation can be used as a prophylactic strategy against mastitis

Age-Related Decline in the Variation of Dynamic Functional Connectivity: A Resting State Analysis

Normal aging is typically characterized by abnormal resting-state functional connectivity (FC), including decreasing connectivity within networks and increasing connectivity between networks, under the assumption that the FC over the scan time was stationary. In fact, the resting-state FC has been shown in recent years to vary over time even within minutes, thus showing the great potential of intrinsic interactions and organization of the brain. In this article, we assumed that the dynamic FC consisted of an intrinsic dynamic balance in the resting brain and was altered with increasing age. Two groups of individuals (N = 36, ages 20–25 for the young group; N = 32, ages 60–85 for the senior group) were recruited from the public data of the Nathan Kline Institute. Phase randomization was first used to examine the reliability of the dynamic FC. Next, the variation in the dynamic FC and the energy ratio of the dynamic FC fluctuations within a higher frequency band were calculated and further checked for differences between groups by non-parametric permutation tests. The results robustly showed modularization of the dynamic FC variation, which declined with aging; moreover, the FC variation of the inter-network connections, which mainly consisted of the frontal-parietal network-associated and occipital-associated connections, decreased. In addition, a higher energy ratio in the higher FC fluctuation frequency band was observed in the senior group, which indicated the frequency interactions in the FC fluctuations. These results highly supported the basis of abnormality and compensation in the aging brain and might provide new insights into both aging and relevant compensatory mechanisms