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1.
Metab Eng ; 64: 122-133, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33577950

RESUMO

Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme involved in numerous physiological processes. As an attractive product in the industrial field, NAD+ also plays an important role in oxidoreductase-catalyzed reactions, drug synthesis, and the treatment of diseases, such as dementia, diabetes, and vascular dysfunction. Currently, although the biotechnology to construct NAD+-overproducing strains has been developed, limited regulation and low productivity still hamper its use on large scales. Here, we describe multi-strategy metabolic engineering to address the NAD+-production bottleneck in E. coli. First, blocking the degradation pathway of NAD(H) increased the accumulation of NAD+ by 39%. Second, key enzymes involved in the Preiss-Handler pathway of NAD+ synthesis were overexpressed and led to a 221% increase in the NAD+ concentration. Third, the PRPP synthesis module and Preiss-Handler pathway were combined to strengthen the precursors supply, which resulted in enhancement of NAD+ content by 520%. Fourth, increasing the ATP content led to an increase in the concentration of NAD+ by 170%. Finally, with the combination of all above strategies, a strain with a high yield of NAD+ was constructed, with the intracellular NAD+ concentration reaching 26.9 µmol/g DCW, which was 834% that of the parent strain. This study presents an efficient design of an NAD+-producing strain through global regulation metabolic engineering.

2.
Microb Cell Fact ; 20(1): 11, 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33422055

RESUMO

BACKGROUND: D-Amino acids are increasingly used as building blocks to produce pharmaceuticals and fine chemicals. However, establishing a universal biocatalyst for the general synthesis of D-amino acids from cheap and readily available precursors with few by-products is challenging. In this study, we developed an efficient in vivo biocatalysis system for the synthesis of D-amino acids from L-amino acids by the co-expression of membrane-associated L-amino acid deaminase obtained from Proteus mirabilis (LAAD), meso-diaminopimelate dehydrogenases obtained from Symbiobacterium thermophilum (DAPDH), and formate dehydrogenase obtained from Burkholderia stabilis (FDH), in recombinant Escherichia coli. RESULTS: To generate the in vivo cascade system, three strategies were evaluated to regulate enzyme expression levels, including single-plasmid co-expression, double-plasmid co-expression, and double-plasmid MBP-fused co-expression. The double-plasmid MBP-fused co-expression strain Escherichia coli pET-21b-MBP-laad/pET-28a-dapdh-fdh, exhibiting high catalytic efficiency, was selected. Under optimal conditions, 75 mg/mL of E. coli pET-21b-MBP-laad/pET-28a-dapdh-fdh whole-cell biocatalyst asymmetrically catalyzed the stereoinversion of 150 mM L-Phe to D-Phe, with quantitative yields of over 99% ee in 24 h, by the addition of 15 mM NADP+ and 300 mM ammonium formate. In addition, the whole-cell biocatalyst was used to successfully stereoinvert a variety of aromatic and aliphatic L-amino acids to their corresponding D-amino acids. CONCLUSIONS: The newly constructed in vivo cascade biocatalysis system was effective for the highly selective synthesis of D-amino acids via stereoinversion.

3.
Food Chem ; 346: 128957, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33460960

RESUMO

During wine consumption, aroma compounds are released from the wine matrix and are transported to the olfactory receptor in vivo, leading to retronasal perception which can affect consumer acceptance. During this process, in addition to the influence of the wine matrix compositions, some physiological factors can significantly influence aroma release leading to altered concentrations of the aroma compounds that reach the receptors. Therefore, this review is focused on the impact of multiple factors, including the physiology and wine matrix, on the aroma released during wine tasting. Moreover, to reflect the pattern of volatiles that reach the olfactory receptors during wine consumption, some analytical approaches have been described for in vitro and in vivo conditions.


Assuntos
Odorantes/análise , Compostos Orgânicos Voláteis/análise , Vinho/análise , Humanos , Espectrometria de Mobilidade Iônica , Microbiota , Boca/microbiologia , Saliva/metabolismo , Paladar , Compostos Orgânicos Voláteis/química
4.
Int J Food Microbiol ; 337: 108933, 2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33181418

RESUMO

Chinese Baijiu is prepared using multiple microbial strains and complex metabolites by simultaneous saccharification and fermentation (SSF). Yeasts are challenged by various endogenous and exogenous factors, detrimentally affecting the ethanol yield. It is imperative to identify and control inhibitory factors. In the present study, microbial taxa and metabolites during Baijiu fermentation were evaluated to identify inhibitors of ethanol production. We found that filamentous fungi and Bacillus, contributing to saccharification, were negatively related to the ethanol content (Spearman's |ρ| > 0.5, P < 0.05). To explore how they affect ethanol production, ten filamentous fungi and three Bacillus strains were isolated. In addition to glucose and maltose, polyols were simultaneously generated by filamentous fungi and Bacillus via the hydrolysis of starch, among which mannitol and erythritol had the highest contents of up to 41.56 ± 2.01 g/kg and 16.16 ± 1.13 g/kg, respectively. The presence of mannitol and erythritol inhibited ethanol production by the functional yeasts Saccharomyces cerevisiae and Pichia kudriavzevii. The presence of 10.0 g/L mannitol significantly (P < 0.01) decreased the ethanol yield of S. cerevisiae by 12.67% (from 39.34 ± 0.02% to 32.71 ± 0.49%). These results revealed that polyols may inhibit the production of Baijiu and other fermented foods, suggesting that the origin and influence of polyols should be a focus of future research.


Assuntos
Eritritol/metabolismo , Etanol/metabolismo , Fermentação , Alimentos e Bebidas Fermentados/microbiologia , Manitol/metabolismo , Humanos , Hidrólise , Pichia/metabolismo , Saccharomyces cerevisiae/metabolismo
5.
Int J Food Microbiol ; 337: 108951, 2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33202299

RESUMO

Pit mud microbiota plays a key role in flavour production for Chinese strong-aroma type liquor. However, the pit mud microbiota cannot be cultured in laboratory. In this study, an oligotrophic medium with acetate as carbon source was used to enrich pit mud microbiota. The 16S rRNA gene amplicon sequencing was applied to examine the microbial dynamics of the enrichment consortia. Both methanogens and bacteria were simultaneously enriched. Euryarchaeota, Bacteroidetes and Firmicutes were the top 3 enriched phyla, and 31 genera were successfully enriched. More specifically, 11 genera (65%) out of the 17 dominant genera in pit mud were successfully enriched, including Petrimonas, Proteiniphilum, Anaerocella, Hydrogenispora, Methanosarcina, Fermentimonas, LNR_A2-18, Sedimentibacter, Lutispora, Syntrophomonas and Aminobacterium. Furthermore, 20 rare genera in the analyzed pit mud samples were also enriched. Aceticlastic Methanosaeta and Methanosarcina were found to be dominant methanogens in the enrichment consortia. Metagenomic sequencing was then applied to the enriched microbial consortia to explore the metabolic potentials of pit mud microbes. Aceticlastic methanogenesis pathway of Methanosaeta was reconstructed. Furthermore, 26 high-quality metagenome-assembled genomes (MAGs) were obtained based on the metagenomic binning analysis. Moreover, nutrients in pit mud were found to be crucial to sustain the methanogenesis of the enriched microbial consortia. These results suggested that the enrichment approach by using oligotrophic culturing can effectively cultivate the pit mud microbiota. Combined with metagenomics, the oligotrophic culturing will be greatly helpful to decipher the community composition and metabolic potentials of pit mud microbiota.


Assuntos
Bebidas Alcoólicas/microbiologia , Microbiota , Acetatos/análise , Acetatos/metabolismo , Archaea/classificação , Archaea/genética , Archaea/isolamento & purificação , Archaea/metabolismo , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , China , Meios de Cultura/química , Fermentação , Humanos , Microbiota/genética , RNA Ribossômico 16S/genética
6.
Eur Respir J ; 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33303530

RESUMO

INTRODUCTION: Early disease morbidity has been associated with asthma persistence in wheezing preschoolers; however, whether asthma control trajectories shortly after diagnosis could influence remission is unknown. We examined the association between asthma control trajectories 2 years post-diagnosis in preschoolers and subsequent disease remission. METHODS: We conducted a multicenter population-based retrospective cohort study consisting of 48 687 children with asthma diagnosed before 5 years old and born between 1990 and 2013 in 4 Canadian provinces who had prolonged disease activity post-diagnosis. Prolonged disease activity was defined as ≥1 medical visit or medication for asthma every 6-month period for ≥4 of the 6 periods post-diagnosis. Follow-up began at 3 years post-diagnosis (at cohort entry). Remission was defined as two consecutive years without drug claims or medical visits for asthma or asthma-like conditions following cohort entry. Asthma control trajectories, ascertained over four 6-month periods following diagnosis using a validated index, were classified as: controlled throughout, improving control, worsening control, out-of-control throughout, and fluctuating control. Adjusted Cox models estimated associations between asthma control trajectories and time-to-remission. A random-effects meta-analysis summarised province-specific Hazard Ratios (HRs). RESULTS: The pooled remission rate was 8.91 (95%CI 8.80,9.02)/100 person-years. Compared to children controlled throughout, poorer asthma control was associated with incrementally lower HRs (95%CI) of remission in 4 other trajectories: improving control, 0.89 (0.82,0.96); fluctuating control, 0.78 (0.71,0.85); worsening control, 0.68 (0.62,0.75); out-of-control throughout, 0.52 (0.45,0.59). CONCLUSIONS: Asthma control trajectories 2 years following a diagnosis in preschool were associated with remission, highlighting the clinical relevance of documenting control trajectories in early life.

7.
Int J Med Sci ; 17(17): 2751-2762, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33162803

RESUMO

Background: To date, the effect of vasopressin on organ damages after acute mesenteric ischemia (MI) remains poorly understood. Aims: To investigate the effect of terlipressin, a selective vasopressin V1 receptor agonist, versus norepinephrine on the intestinal and renal injuries after acute MI, and to explore the underlying mechanism of terlipressin. Methods: Acute MI model was produced by clamping the superior mesenteric artery for 1 hour. Immediately after unclamping, terlipressin or norepinephrine was intravenously administered for 2 hours. Meanwhile, in vitro, RAW264.7 cells were treated with lipopolysaccharide or lipopolysaccharide+terlipressin. In addition, wortmannin was used to determine the role of phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway in the potential impacts of terlipressin. Results: MI led to severe hypotension, caused notable intestinal and renal impairments and resulted in high mortality, which were markedly improved by terlipressin or norepinephrine. Terlipressin increased mean arterial pressure, decreased intestinal epithelial cell apoptosis, inhibited the generation of M1 macrophage in intestinal and renal tissues, and hindered the release of inflammatory cytokines after MI. Moreover, in cultured macrophages, terlipressin reduced the mRNA level of specific M1 markers and the release of inflammatory cytokines caused by lipopolysaccharide challenge. Wortmannin decreased the expression of PI3K and Akt induced by terlipressin in cells and in tissues, and abolished the above protective effects conferred by terlipressin. Conclusions: Terlipressin or norepinephrine could effectively improve organ damages and mortality after acute MI. Terlipressin elevates blood pressure and inhibits intestinal epithelial apoptosis and macrophage M1 polarization via the PI3K/Akt pathway.

8.
Int J Mol Sci ; 21(15)2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32731373

RESUMO

Fe(II)/2-ketoglutarate-dependent dioxygenase (Fe(II)/2-KG DO)-mediated hydroxylation is a critical type of C-H bond functionalization for synthesizing hydroxy amino acids used as pharmaceutical raw materials and precursors. However, DO activity requires 2-ketoglutarate (2-KG), lack of which reduces the efficiency of Fe(II)/2-KG DO-mediated hydroxylation. Here, we conducted multi-enzymatic syntheses of hydroxy amino acids. Using (2s,3r,4s)-4-hydroxyisoleucine (4-HIL) as a model product, we coupled regio- and stereo-selective hydroxylation of l-Ile by the dioxygenase IDO with 2-KG generation from readily available l-Glu by l-glutamate oxidase (LGOX) and catalase (CAT). In the one-pot system, H2O2 significantly inhibited IDO activity and elevated Fe2+ concentrations of severely repressed LGOX. A sequential cascade reaction was preferable to a single-step process as CAT in the former system hydrolyzed H2O2. We obtained 465 mM 4-HIL at 93% yield in the two-step system. Moreover, this process facilitated C-H hydroxylation of several hydrophobic aliphatic amino acids to produce hydroxy amino acids, and C-H sulfoxidation of sulfur-containing l-amino acids to yield l-amino acid sulfoxides. Thus, we constructed an efficient cascade reaction to produce 4-HIL by providing prerequisite 2-KG from cheap and plentiful l-Glu and developed a strategy for creating enzymatic systems catalyzing 2-KG-dependent reactions in sustainable bioprocesses that synthesize other functional compounds.

9.
mSystems ; 5(4)2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32694129

RESUMO

We are rapidly increasing our understanding on the spatial distribution of microbial communities. However, microbial functioning, as well as temporal differences and mechanisms causing microbial community shifts, remains comparably little explored. Here, using Chinese liquor fermentation as a model system containing a low microbial diversity, we studied temporal changes in microbial community structure and functioning. For that, we used high-throughput sequencing to analyze the composition of bacteria and fungi and analyzed the microbially derived metabolome throughout the fermentation process in all four seasons in both 2018 and 2019. We show that microbial communities and the metabolome changed throughout the fermentation process in each of the four seasons, with metabolome diversity increasing throughout the fermentation process. Across seasons, bacterial and fungal communities as well as the metabolome driven by 10 indicator microorganisms and six metabolites varied even more. Daily average temperature in the external surroundings was the primary determinant of the observed temporal microbial community and metabolome changes. Collectively, our work reveals critical insights into patterns and processes determining temporal changes of microbial community composition and functioning. We highlight the importance of linking taxonomic to functional changes in microbial ecology to enable predictions of human-relevant applications.IMPORTANCE We used Chinese liquor fermentation as a model system to show that microbiome composition changes more dramatically across seasons than throughout the fermentation process within seasons. These changes translate to differences in the metabolome as the ultimate functional outcome of microbial activity, suggesting that temporal changes in microbiome composition are translating into functional changes. This result is striking as it suggests that microbial functioning, despite controlled conditions in the fermentors, fluctuates over season along with external temperature differences, which threatens a reproducible food taste. As such, we believe that our study provides a stepping-stone into novel taxonomy-functional studies that promote future work in other systems and that also is relevant in applied settings to better control surrounding conditions in food production.

10.
Phys Chem Chem Phys ; 22(28): 16007-16012, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32632421

RESUMO

A strong built-in electric field, high carrier mobility and a wide range of optical absorption values are the key parameters for photocatalysts used in water splitting. The design and preparation of photocatalysts possessing simultaneously these characteristics have always been the main tasks in the water splitting field. Here, we report a new family of 2D Na-based photocatalysts, NaAB2 (A = Al, Ga, In; B = S, Se, Te) monolayers, which may achieve this goal. First-principles calculations show that most of the NaAB2 monolayers are semiconductors with a suitable direct band gap ranging from visible to near-infrared light, exhibiting good optical absorption. The electron mobilities of the NaAB2 monolayers are up to 103 cm2 V-1 s-1, meaning the rapid migration of electrons can promote photocatalytic overall water splitting. Importantly, the electrostatic potential differences between the top surface and the bottom surface are larger than 1.23 eV for all the studied NaAB2 monolayers, meaning a high intrinsic built-in electric field that is present in these Na-based photocatalysts can promote the overall water splitting irrespective of their band gaps and band edges. Our studies show that the NaAB2 monolayers may be ideal photocatalysts for use in water splitting and may initiate a new round of experimental studies.

11.
Appl Microbiol Biotechnol ; 104(17): 7551-7562, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32632476

RESUMO

Pullulanases are widely used in food, medicine, and other industries because they specifically hydrolyze α-1,6-glycosidic linkages in starch and oligosaccharides. In addition, high-temperature thermostable pullulanase has multiple advantages, including decreasing saccharification solution viscosity accompanied with enhanced mass transfer and reducing microbial contamination in starch hydrolysis. However, thermophilic pullulanase availability remains limited. Additionally, most do not meet starch-manufacturing requirements due to weak thermostability. Here, we developed a computation-aided strategy to engineer the thermophilic pullulanase from Bacillus thermoleovorans. First, three computational design predictors (FoldX, I-Mutant 3.0, and dDFIRE) were combined to predict stability changes introduced by mutations. After excluding conserved and catalytic sites, 17 mutants were identified. After further experimental verification, we confirmed six positive mutants. Among them, the G692M mutant had the highest thermostability improvement, with 3.8 °C increased Tm and 2.1-fold longer half-life than the wild type at 70 °C. We then characterized the mechanism underlying increased thermostability, such as rigidity enhancement, closer conformation, and strengthened motion correlation using root mean square fluctuation (RMSF), principal component analysis (PCA), dynamic cross-correlation map (DCCM), and free energy landscape (FEL) analysis. KEY POINTS: • A computation-aided strategy was developed to engineer pullulanase thermostability. • Seventeen mutants were identified by combining three computational design predictors. • The G692M mutant was obtained with increased Tmand half-life at 70 °C.

12.
Infect Drug Resist ; 13: 2053-2061, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636658

RESUMO

Purpose: Although immune dysfunction has been investigated in adult septic patients, early immune status remains unclear. In this study, our primary aim was to assess early immune status in adult patients with sepsis stratified by age and its relevance to hospital mortality. Patients and Methods: A post hoc analysis of a multicenter, randomized controlled trial was conducted; 273 patients whose immune status was evaluated within 48 hours after onset of sepsis were enrolled. Early immune status was evaluated by the percentage of monocyte human leukocyte antigen-DR (mHLA-DR) in total monocytes within 48 hours after onset of sepsis and it was classified as immunoparalysis (mHLA-DR ≤30%) or non-immunoparalysis (>30%). Three logistic regression models were conducted to explore the associations between early immunoparalysis and hospital mortality. We also developed two sensitivity analyses to find out whether the definition of early immune status (24 hours vs 48 hours after onset of sepsis) and immunotherapy affect the primary outcome. Results: Of the 181 elderly (≥60yrs) and 92 non-elderly (<60yrs) septic patients, 71 (39.2%) and 25 (27.2%) died in hospital, respectively. The percentage of early immunoparalysis in the elderly was twice of that in the non-elderly patients (32% vs 16%, p=0.006). For the elderly, hospital mortality was higher in the immunoparalysis ones than the non-immunoparalysis ones (53.4% vs 32.5%, p=0.009). But there was no significant difference in hospital mortality between immunoparalysis non-elderly patients and non-immunoparalysis non-elderly ones (33.5% vs 26.0%, p=0.541). By means of logistic regression models, we found that early immunoparalysis was independently associated with increased hospital mortality in elderly, but not in non-elderly patients. Sensitivity analysis further confirmed the definition of early immune status and immunotherapy did not affect the outcomes. Conclusion: The elderly were more susceptible to early immunoparalysis after onset of sepsis. Early immunoparalysis was independently associated with poor prognosis in elderly, but not in non-elderly patients.

13.
Crit Care Med ; 48(8): e675-e683, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32697508

RESUMO

OBJECTIVE: To estimate incidence of newly diagnosed mental disorders among ICU patients. DESIGN: Retrospective-matched cohort study using a population-based administrative database. SETTING: Manitoba, Canada. PARTICIPANTS: A total of 49,439 ICU patients admitted between 2000 and 2012 were compared with two control groups (hospitalized: n = 146,968 and general population: n = 141,937), matched on age (± 2 yr), sex, region of residence, and hospitalization year. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Incident mental disorders (mood, anxiety, substance use, personality, posttraumatic stress disorder, schizophrenia, and psychotic disorders) not diagnosed during the 5-year period before the index ICU or hospital admission date (including matched general population group), but diagnosed during the subsequent 5-year period. Multivariable survival models adjusted for sociodemographic variables, Charlson comorbidity index, admission diagnostic category, and number of ICU and non-ICU exposures. ICU cohort had a 14.5% (95% CI, 14.0-15.0) and 42.7% (95% CI, 42.0-43.5) age- and sex-standardized incidence of any diagnosed mental disorder at 1 and 5 years post-ICU exposure, respectively. In multivariable analysis, ICU cohort had increased risk of any diagnosed mental disorder at all time points versus the hospitalized cohort (year 5: adjusted hazard ratio, 2.00; 95% CI, 1.80-2.23) and the general population cohort (year 5: adjusted hazard ratio, 3.52; 95% CI, 3.23-3.83). A newly diagnosed mental disorder was associated with younger age, female sex, more recent admitting years, presence of preexisting comorbidities, and repeat ICU admission. CONCLUSIONS: ICU admission is associated with an increased incidence of mood, anxiety, substance use, and personality disorders over a 5-year period.

14.
Microb Cell Fact ; 19(1): 125, 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32513165

RESUMO

BACKGROUND: Deracemization, the transformation of the racemate into a single stereoisomeric product in 100% theoretical yield, is an appealing but challenging option for the asymmetric synthesis of optically pure chiral compounds as important pharmaceutical intermediates. To enhance the synthesis of (R)-1,3-butanediol from the corresponding low-cost racemate with minimal substrate waste, we designed a stereoinverting cascade deracemization route and constructed the cascade reaction for the total conversion of racemic 1,3-butanediol into its (R)-enantiomer. This cascade reaction consisted of the absolutely enantioselective oxidation of (S)-1,3-butanediol by Candida parapsilosis QC-76 and the subsequent asymmetric reduction of the intermediate 4-hydroxy-2-butanone to (R)-1,3-butanediol by Pichia kudriavzevii QC-1. RESULTS: The key reaction conditions including choice of cosubstrate, pH, temperature, and rotation speed were optimized systematically and determined as follows: adding acetone as the cosubstrate at pH 8.0, a temperature of 30 °C, and rotation speed of 250 rpm for the first oxidation process; in the next reduction process, the optimal conditions were: adding glucose as the cosubstrate at pH 8.0, a temperature of 35 °C, and rotation speed of 200 rpm. By investigating the feasibility of the step-by-step method with one-pot experiment as a natural extension for performing the oxidation-reduction cascade, the step-by-step approach exhibited high efficiency for this cascade process from racemate to (R)-1,3-butanediol. Under optimal conditions, 20 g/L of the racemate transformed into 16.67 g/L of (R)-1,3-butanediol with 99.5% enantiomeric excess by the oxidation-reduction cascade system in a 200-mL bioreactor. CONCLUSIONS: The step-by-step cascade reaction efficiently produced (R)-1,3-butanediol from the racemate by biosynthesis and shows promising application prospects.

15.
Crit Care Med ; 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32541566

RESUMO

OBJECTIVE: To estimate incidence of newly diagnosed mental disorders among ICU patients. DESIGN: Retrospective-matched cohort study using a population-based administrative database. SETTING: Manitoba, Canada. PARTICIPANTS: A total of 49,439 ICU patients admitted between 2000 and 2012 were compared with two control groups (hospitalized: n = 146,968 and general population: n = 141,937), matched on age (± 2 yr), sex, region of residence, and hospitalization year. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Incident mental disorders (mood, anxiety, substance use, personality, posttraumatic stress disorder, schizophrenia, and psychotic disorders) not diagnosed during the 5-year period before the index ICU or hospital admission date (including matched general population group), but diagnosed during the subsequent 5-year period. Multivariable survival models adjusted for sociodemographic variables, Charlson comorbidity index, admission diagnostic category, and number of ICU and non-ICU exposures. ICU cohort had a 14.5% (95% CI, 14.0-15.0) and 42.7% (95% CI, 42.0-43.5) age- and sex-standardized incidence of any diagnosed mental disorder at 1 and 5 years post-ICU exposure, respectively. In multivariable analysis, ICU cohort had increased risk of any diagnosed mental disorder at all time points versus the hospitalized cohort (year 5: adjusted hazard ratio, 2.00; 95% CI, 1.80-2.23) and the general population cohort (year 5: adjusted hazard ratio, 3.52; 95% CI, 3.23-3.83). A newly diagnosed mental disorder was associated with younger age, female sex, more recent admitting years, presence of preexisting comorbidities, and repeat ICU admission. CONCLUSIONS: ICU admission is associated with an increased incidence of mood, anxiety, substance use, and personality disorders over a 5-year period.

16.
Shock ; 54(6): 751-760, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32433213

RESUMO

BACKGROUND: We performed a systematic review and meta-analysis of studies investigating the end-expiratory occlusion (EEO) test induced changes in cardiac index (CI) and in arterial pressure as predictors of fluid responsiveness in adults receiving mechanical ventilation. METHODS: MEDLINE, EMBASE, Cochrane Database, and Chinese database were screened for relevant original and review articles. The meta-analysis determined the pooled sensitivity, specificity, diagnostic odds ratio, area under the receiver operating characteristic curve (AUROC), and threshold for the EEO test assessed with CI and arterial pressure. In addition, heterogeneity and subgroup analyses were performed. RESULTS: We included 13 studies involving 479 adult patients and 523 volume expansion. Statistically significant heterogeneity was identified, and meta-regression indicated that prone position was the major sources of heterogeneity. After removal of the study performed in prone position, heterogeneity became nonsignificant. EEO-induced changes in CI (or surrogate) are accurate for predicting fluid responsiveness in semirecumbent or supine patients, with excellent pooled sensitivity of 92% (95% CI, 0.88-0.95, I = 0.00%), specificity of 89% (95% CI, 0.83-0.93, I = 34.34%), and a summary AUROC of 0.95 (95% CI, 0.93-0.97). The mean threshold was an EEO-induced increase in CI (or surrogate) of more than 4.9 ± 1.5%. EEO test exhibited better diagnostic performance in semirecumbent or supine patients than prone patients, with higher AUROC (0.95 vs. 0.65; P < 0.001). In addition, EEO test exhibited higher specificity (0.93 vs. 0.83, P < 0.001) in patients ventilated with low tidal volume compared with normal or nearly normal tidal volume. However, EEO test was less accurate when its hemodynamic effects were detected on arterial pressure. EEO-induced changes in arterial pressure exhibited a lower sensitivity (0.88 vs. 0.92; P = 0.402), specificity (0.77 vs. 0.90; P = 0.019), and AUROC (0.87 vs. 0.96; P < 0.001) compared with EEO-induced changes in CI (or surrogate). CONCLUSIONS: EEO test is accurate to predict fluid responsiveness in semirecumbent or supine patients but not in prone patients. EEO test exhibited higher specificity in patients ventilated with low tidal volume, and its accuracy is better when its hemodynamic effects are assessed by direct measurement of CI than by the arterial pressure.

17.
Zhongguo Zhong Yao Za Zhi ; 45(1): 142-148, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237423

RESUMO

The aim of this paper was to observe the effect of Realgar and arsenic trioxide on gut microbiota. The mice were divided into low-dose Realgar group(RL), medium-dose Realgar group(RM), high-dose Realgar group(RH), and arsenic trioxide group(ATO), in which ATO and RL groups had the same trivalent arsenic content. Realgar and arsenic trioxide toxicity models were established after intragastric administration for 1 week, and mice feces were collected 1 h after intragastric administration on day 8. The effects of Realgar on gut microbiota of mice were observed through bacterial 16 S rRNA gene sequences. The results showed that Lactobacillus was decreased in all groups, while Ruminococcus and Adlercreutzia were increased. The RL group and ATO group were consistent in the genera of Prevotella, Ruminococcus, and Adlercreutzia but different in the genera of Lactobacillus and Bacteroides. Therefore, the effects of Realgar and arsenic trioxide with the same amount of trivalent arsenic on gut microbiota were similar, but differences were still present. Protective bacteria such as Lactobacillus were reduced after Realgar administration, causing inflammation. At low doses, the number of anti-inflammatory bacteria, such as Ruminococcus, Adlercreutzia and Parabacteroides increased, which can offset the slight inflammation caused by the imbalance of bacterial flora. At high doses, the flora was disturbed and the number of Proteobacteria was increased, with aggravated intestinal inflammation, causing edema and other inflammatory reactions. Based on this, authors believe that the gastrointestinal reactions after clinical use of Realgar may be related to flora disorder. Realgar should be used at a small dose in combination with other drugs to reduce intestinal inflammation.


Assuntos
Trióxido de Arsênio/farmacologia , Arsenicais/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Sulfetos/farmacologia , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Camundongos
18.
Food Res Int ; 131: 109043, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32247503

RESUMO

An analytical method based on headspace solid-phase microextraction (HS-SPME) combined with comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOFMS) was developed to characterize volatile sulfur compounds (VSCs) in soy sauce aroma type Baijiu (SSAB) and soy sauce aroma type rounds Baijiu (SSARB). Using this method, 19 VSCs were identified and quantified. The aroma contribution of VSCs was evaluated by odor activity values (OAVs) and perceptive interactions. Seven VSCs had concentrations higher than their corresponding odor thresholds. In particular, the presence of methyl furfuryl disulfide (OAV: 7-11) and 2-methyl-3-(methyldisulfanyl)furan (OAV: 9-18) with relatively high OAVs in Baijiu was reported for the first time, and they could be the important aroma contributors to SSAB. Moreover, sensory analysis revealed that dimethyl sulfide, dimethyl disulfide, and dimethyl trisulfide enhanced the perception of fruity aromas in the matrices studied. Partial least-squares discriminant analysis (PLS-DA) analysis indicated that the VSCs could be used to distinguish SSARB.

19.
3 Biotech ; 10(4): 167, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32206501

RESUMO

l-isoleucine dioxygenase (IDO) is an Fe (II)/α-ketoglutarate (α-KG)-dependent dioxygenase that specifically converts l-isoleucine (l-Ile) to (2S, 3R, 4S)-4-hydroxyisoleucine (4-HIL). 4-HIL is an important drug for the treatment and prevention of type 1 and type 2 diabetes but the yields using current methods are low. In this study, the CRISPR-Cas9 gene editing system was used to knockout sucAB and aceAK gene in the TCA cycle pathway of Escherichia coli (E. coli). For single-gene knockout, the whole process took approximately 7 days. However, the manipulation time was reduced by 2 days for each round of gene modification for multigene editing. Using the genome-edited recombinant strain E. coli BL21(DE3) ΔsucABΔaceAK/pET-28a(+)-ido (2Δ-ido), the bioconversion ratio of L-Ile to 4-HIL was enhanced by about 15% compared to E. coli BL21(DE3)/pET-28a(+)-ido [BL21(DE3)-ido] strain. The CRISPR-Cas9 editing strategy has the potential in modifying multiple genes more rapidly and in optimizing strains for industrial production.

20.
AMB Express ; 10(1): 11, 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31955316

RESUMO

Pullulanase is an important starch-debranching enzyme mostly used in starch processing-related food industries. However, the levels of pullulanase produced from recombinant Bacillus subtilis, a Generally Recognized as Safe (GRAS) host, are generally limited. To enhance the activity of pullulanase, batch fermentation and fed-batch fermentation were systematically investigated. The overall purpose is to improve the fermentation yield by optimizing the feeding strategy in the fermentation process, thereby increasing the enzyme activity of pullulanase. Therefore, in this study, the feeding methods, the feeding ingredients, the feeding concentration, and pH values were studied in detail. The optimized fermentation conditions for pullulanase production from recombinant B. subtilis were determined as following: inoculum volume 7%, pH 6.5, the dissolved oxygen level 30%, and constant-rate feeding of 100 mL glucose solution (400 g L-1) in late logarithmic growth. The OD600 of recombinant B. subtilis and enzyme activity were 84.54 and 102.75 U mL-1, which were respectively 141% and 144% higher than that before optimization. These findings provided a prerequisite for further amplification of the fermentation system to obtain higher enzyme activity.

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