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In this review, for the first time, we discussed current highlights in the mechanism of MGRS-related lesions.PURPOSE Occurrence of tinnitus can be, for a person who experiences it, a disorder affecting the overall equilibrium of the organism. To cope with it a variety of personal resources, such as positive orientation and basic hope, are mobilized. The aim of this study was to determine whether these resources are associated with the evaluation of the impact of tinnitus on the functioning of the study participants. METHODS Study involved 176 tinnitus sufferers, including 123 women and 53 men. The results were compiled using Positivity Scale (P-scale) for measuring positive orientation, Basic Hope Inventory (BHI-R) for measuring basic hope, the questionnaires Tinnitus Handicap Inventory (THI) and Tinnitus Functional Index (TFI) evaluating the impact of tinnitus on the daily functioning of the subjects, as well as a survey designed for the study, comprising questions about sociodemographic data and tinnitus history. RESULTS Results of regression analysis indicated that positive orientation is the most important for the perceived tinnitus annoyance. However, no significant influence of basic hope on tinnitus annoyance was found. Among other variables taken into account in regression analysis, age and presence of additional diseases proved to be important predictors of tinnitus annoyance. CONCLUSIONS Personality determinants (positive orientation) are related to the perception of tinnitus annoyance. When working with a tinnitus patient, it is justified to pay attention to the existence of the positive orientation and to work on its development. Research should also be continued to search for other personal resources that affect the perceived tinnitus annoyance.The prognostic implications of cardiovascular magnetic resonance imaging (CMR)-derived hyperemic myocardial blood flow (MBF) in patients with ST-elevation myocardial infarction (STEMI) are unknown. This study sought to investigate the incremental prognostic value of hyperemic MBF over conventional CMR markers to identify patients with high risk of future incidence of patient-oriented composite outcomes (POCO) and major adverse cardiac events (MACE) after STEMI. A total of 237 patients who presented with STEMI were prospectively enrolled. The CMR protocol included left-ventricular ejection fraction (LVEF), late gadolinium enhancement (LGE) and microvascular obstruction (MVO) measurement, and volumetric MBF assessment. During a median follow-up of 2.6 years, 47 patients experienced POCO (primary outcome) and 21 patients had MACE. In a multivariable model, multivessel disease, LGE, MVO, and hyperemic MBF were independently associated with POCO. Addition of hyperemic MBF to the model consisting of GRACE score, multivessel disease, LVEF, LGE, and MVO significantly improved the predictive efficacy (integrated discrimination improvement 0.020, p = 0.021). Patients with low hyperemic MBF had significantly higher incidence of MACE compared to those with high hyperemic MBF in propensity score matching analysis (p = 0.018). In conclusion, CMR-derived hyperemic MBF could provide independent and incremental prognostic value over LVEF, LGE, and MVO in patients with STEMI.PURPOSE Validated biomarkers of food intake (BFIs) have recently been suggested as a useful tool to assess adherence to dietary guidelines or compliance in human dietary interventions. Although many new candidate biomarkers have emerged in the last decades for different foods from metabolic profiling studies, the number of comprehensively validated biomarkers of food intake is limited. Apples are among the most frequently consumed fruits and a rich source of polyphenols and fibers, an important mediator for their health-protective properties. METHODS Using an untargeted metabolomics approach, we aimed to identify biomarkers of long-term apple intake and explore how apples impact on the human plasma and urine metabolite profiles. Forty mildly hypercholesterolemic volunteers consumed two whole apples or a sugar and energy-matched control beverage, daily for 8 weeks in a randomized, controlled, crossover intervention study. The metabolome in plasma and urine samples was analyzed via untargeted metabolomics. RESUol microbial metabolites suggests that apple consumption mediates significant gut microbial metabolic activity which should be further explored.γ-Glutamylcysteine synthetase (γ-GCS) from Escherichia coli, which catalyzes the formation of L-glutamylcysteine from L-glutamic acid and L-cysteine, was engineered into an L-theanine synthase using L-glutamic acid and ethylamine as substrates. A high-throughput screening method using a 96-well plate was developed to evaluate the L-theanine synthesis reaction. Both site-saturation mutagenesis and random mutagenesis were applied. PLX-4720 molecular weight After three rounds of directed evolution, 13B6, the best-performing mutant enzyme, exhibited 14.6- and 17.0-fold improvements in L-theanine production and catalytic efficiency for ethylamine, respectively, compared with the wild-type enzyme. In addition, the specific activity of 13B6 for the original substrate, L-cysteine, decreased to approximately 14.6% of that of the wild-type enzyme. Thus, the γ-GCS enzyme was successfully switched to a specific L-theanine synthase by directed evolution. Furthermore, an ATP-regeneration system was introduced based on polyphosphate kinases catalyzing the transfer of phosphates from polyphosphate to ADP, thus lowering the level of ATP consumption and the cost of L-theanine synthesis. The final L-theanine production by mutant 13B6 reached 30.4 ± 0.3 g/L in 2 h, with a conversion rate of 87.1%, which has great potential for industrial applications.Dyeing methods that conform to environmental protection requirements and adapt to the development of industry are investigated using bleached poplar wood dyed with melanin secreted by Lasiodiplodia theobromae in this paper. Prolonging the dyeing time of coarse melanin can improve the dye uptake of veneers, and the brightness value increases, and the reflectivity declines with the increase of dyeing time. The stained surface of the vessel is gradually covered by coarse melanin dye, and more melanin particles can be clearly observed accumulating together on the stained surface with agar. Infrared measurements show that the absorption peak of -C=O in carboxylic acid disappears at 1740 cm-1, which can be attributed to the fact that -C=O (1776 cm-1) in an anhydride or ketone group is formed by further oxidation and condensation of agar and NaOH. The veneer dyed for 6 h showed a well light and water resistance. Additionally, dyeing can improve the wettability of water, phenolic resin, and urea formaldehyde resin on the surface of veneer. These results support the use of pigment secreted by stain fungi for wood and provide data for evaluating their use as sustainable materials for other applications.The cytochrome P450 monooxygenase RosC catalyzes the three-step oxidation reactions, which leads to the formation of a hydroxy, formyl, and carboxy group at C-20 during rosamicin biosynthesis in Micromonospora rosaria IFO13697. To determine if amino acid substitutions in RosC could allow for the control of the multistep oxidation reactions, we screened RosC random mutants. The RosC mutant RM30, with five amino acid substitutions (P107S, L176Q, S254N, V277A, and I319N), catalyzed only the first step of the oxidation reaction. Whole-cell assays using Escherichia coli cells expressing RosC mutants with single and double amino acid substitutions derived from RM30 indicated that P107S/L176Q, P107S/V277A, P107S/I319N, L176Q/V277A, L176Q/I319N, and S254N/V277A significantly reduced the catalytic activity of the second reaction, which is alcohol oxidation. Of the previously mentioned mutants, double mutants containing L176Q, which was presumed to occur in the FG loop region, lost the total catalytic activity of the third reaction (aldehyde oxidation). Additionally, an engineered M. rosaria strain with rosC disruption, which introduced the gene encoding the RosC mutants P107S/L176Q and P107S/V277A preferentially produced 20-dihydrorosamicin, which is formed after the first oxidation reaction of RosC.Alginate oligosaccharides are associated with some beneficial health effects. Gut microbiota is one of the most recently identified factors in the development of several metabolic diseases induced by high-fat diet. Our objective was to evaluate how alginate oligosaccharides impact on high-fat diet‑induced features of metabolic disorders and whether this impact is related to modulations in the modulation of the gut microbiota. C57BL/6J mice were fed with chow diet, high-fat diet, or high-fat diet supplemented with alginate oligosaccharides for 10 weeks. Alginate oligosaccharide treatment improved lipid metabolism, such as reducing levels of TG and LDL-C and inhibiting expression of lipogenesis genes. Alginate oligosaccharide administration reduced the levels of fasting blood glucose and increased the levels of serum insulin. Alginate oligosaccharide treatment was found to lower the expression of markers of inflammation, including IL1β and CD11c. Alginate oligosaccharide treatment modulated gut microbial communities and markedly prompted the growth of Akkermansia muciniphila, Lactobacillus reuteri, and Lactobacillus gasseri. Additionally, alginate oligosaccharide intervention significantly increased concentrations of short-chain fatty acids, such as acetic acid, propionic acid, and butyric acid, as well as decreased levels of endotoxin. Alginate oligosaccharides exert beneficial effects via alleviating metabolic metrics induced by high-fat diet, which is associated with increase in A. muciniphila, L. reuteri, and L. gasseri, as well as the release of microbiota-dependent short-chain fatty acids and inhibition of endotoxin levels.The industrial yeast Saccharomyces cerevisiae has a plastic genome with a great flexibility in adaptation to varied conditions of nutrition, temperature, chemistry, osmolarity, and pH in diversified applications. A tolerant strain against 2-furaldehyde (furfural) and 5-hydroxymethyl-2-furaldehyde (HMF) was successfully obtained previously by adaptation through environmental engineering toward development of the next-generation biocatalyst. Using a time-course comparative transcriptome analysis in response to a synergistic challenge of furfural-HMF, here we report tolerance phenotypes of pathway-based transcriptional profiles as components of the adapted defensive system for the tolerant strain NRRL Y-50049. The newly identified tolerance phenotypes were involved in biosynthesis superpathway of sulfur amino acids, defensive reduction-oxidation reaction process, cell wall response, and endogenous and exogenous cellular detoxification. Key transcription factors closely related to these pathway-based components, such as Yap1, Met4, Met31/32, Msn2/4, and Pdr1/3, were also presented. Many important genes in Y-50049 acquired an enhanced transcription background and showed continued increased expressions during the entire lag phase against furfural-HMF. Such signature expressions distinguished tolerance phenotypes of Y-50049 from the innate stress response of its progenitor NRRL Y-12632, an industrial type strain. The acquired yeast tolerance is believed to be evolved in various mechanisms at the genomic level. Identification of legitimate tolerance phenotypes provides a basis for continued investigations on pathway interactions and dissection of mechanisms of yeast tolerance and adaptation at the genomic level.