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Metabolic Engineering Jun 2024Vitamin B [D-pantothenic acid (D-PA)] is an essential water-soluble vitamin that is widely used in the food and feed industries. Currently, the relatively low...
Vitamin B [D-pantothenic acid (D-PA)] is an essential water-soluble vitamin that is widely used in the food and feed industries. Currently, the relatively low fermentation efficiency limits the industrial application of D-PA. Here, a plasmid-free D-PA hyperproducer was constructed using systematic metabolic engineering strategies. First, pyruvate was enriched by deleting the non-phosphotransferase system, inhibiting pyruvate competitive branches, and dynamically controlling the TCA cycle. Next, the (R)-pantoate pathway was enhanced by screening the rate-limiting enzyme PanBC and regulating the other enzymes of this pathway one by one. Then, to enhance NADPH sustainability, NADPH regeneration was achieved through the novel "PEACES" system by (1) expressing the NAD kinase gene ppnk from Clostridium glutamicum and the NADP-dependent gapC from Clostridium acetobutyricum and (2) knocking-out the endogenous sthA gene, which interacts with ilvC and panE in the D-PA biosynthesis pathway. Combined with transcriptome analysis, it was found that the membrane proteins OmpC and TolR promoted D-PA efflux by increasing membrane fluidity. Strain PA132 produced a D-PA titer of 83.26 g/L by two-stage fed-batch fermentation, which is the highest D-PA titer reported so far. This work established competitive producers for the industrial production of D-PA and provided an effective strategy for the production of related products.
PubMed: 38942195
DOI: 10.1016/j.ymben.2024.06.006 -
International Journal of Molecular... Jun 2024, a microalga known for its photosynthetic efficiency, serves as a cell factory, producing valuable biomolecules such as proteins, lipids, and pigments. These components...
, a microalga known for its photosynthetic efficiency, serves as a cell factory, producing valuable biomolecules such as proteins, lipids, and pigments. These components make it an ideal candidate for biofuel production and pharmaceutical applications. In this study, we genetically engineered to overexpress the enzyme fructose-1,6-bisphosphatase (cyFBPase) using the Hsp promoter, aiming to enhance sugar metabolism and biomass accumulation. The modified algal strain, termed NgFBP, exhibited a 1.34-fold increase in cyFBPase activity under photoautotrophic conditions. This modification led to a doubling of biomass production and an increase in eicosapentaenoic acid (EPA) content in fatty acids to 20.78-23.08%. Additionally, the genetic alteration activated the pathways related to glycine, protoporphyrin, thioglucosides, pantothenic acid, CoA, and glycerophospholipids. This shift in carbon allocation towards chloroplast development significantly enhanced photosynthesis and growth. The outcomes of this study not only improve our understanding of photosynthesis and carbon allocation in but also suggest new biotechnological methods to optimize biomass yield and compound production in microalgae.
Topics: Photosynthesis; Fructose-Bisphosphatase; Stramenopiles; Microalgae; Metabolomics; Biomass; Cytosol
PubMed: 38928505
DOI: 10.3390/ijms25126800 -
Zhongguo Dang Dai Er Ke Za Zhi =... Jun 2024To study the characteristics and clinical value of intestinal metabolites in children aged 4-6 years with obstructive sleep apnea-hypopnea syndrome (OSAHS).
OBJECTIVES
To study the characteristics and clinical value of intestinal metabolites in children aged 4-6 years with obstructive sleep apnea-hypopnea syndrome (OSAHS).
METHODS
A total of 31 children aged 4-6 years with OSAHS were prospectively enrolled as the test group, and 24 healthy children aged 4-6 years were included as the control group. Relevant clinical indicators were recorded. Fecal samples were collected, and non-targeted metabolomics analysis using liquid chromatography-mass spectrometry was performed to detect all metabolites.
RESULTS
A total of 206 metabolites were detected, mainly amino acids and their derivatives. There was a significant difference in the overall composition of intestinal metabolites between the test and control groups (<0.05). Eighteen different metabolites were selected, among which six (N-acetylmethionine, L-methionine, L-lysine, DL-phenylalanine, L-tyrosine, and L-isoleucine) had receiver operating characteristic curve areas greater than 0.7 for diagnosing OSAHS. Among them, N-acetylmethionine had the largest area under the curve, which was 0.807, with a sensitivity of 70.83% and a specificity of 80.65%. Correlation analysis between different metabolites and clinical indicators showed that there were positive correlations between the degree of tonsil enlargement and enterolactone, between uric acid and phenylacetaldehyde, between blood glucose and acetylmethionine, and between cholesterol and 9-bromodiphenyl and procaine (<0.05). There were negative correlations between the degree of tonsil enlargement and N-methyltyramine, aspartate aminotransferase and indolepropionic acid and L-isoleucine, between alanine aminotransferase and DL-phenylalanine, between indolepropionic acid and L-isoleucine, between uric acid and hydroxyquinoline, and between urea nitrogen and N,N-dicyclohexylurea (<0.05). The metabolic functional pathways affected by differential metabolites mainly included riboflavin metabolism, arginine and proline metabolism, pantothenic acid and coenzyme A biosynthesis, cysteine and methionine metabolism, lysine degradation and glutathione metabolism.
CONCLUSIONS
Intestinal metabolites and metabolic functions are altered in children aged 4-6 years with OSAHS, primarily involving amino acid metabolism disorders. The screened differential intestinal metabolites have potential screening and diagnostic value as biomarkers for OSAHS.
Topics: Humans; Child; Male; Child, Preschool; Female; Sleep Apnea, Obstructive; Intestines; Methionine
PubMed: 38926373
DOI: 10.7499/j.issn.1008-8830.2309129 -
International Journal For Vitamin and... Jun 2024Attention deficit hyperactivity disorder (ADHD) is a common childhood neurodevelopmental disorder that begins before age 12. Given the role of B group vitamins in cell... (Meta-Analysis)
Meta-Analysis Review
Attention deficit hyperactivity disorder (ADHD) is a common childhood neurodevelopmental disorder that begins before age 12. Given the role of B group vitamins in cell metabolism, synthesis of nucleotides, and neurotransmitters, the present study systematically investigated the plasma levels of vitamins B and B in children with ADHD. We searched electronic databases including Web of Science, MEDLINE, EMBASE, Scopus, Iran MEDEX, Cochran database, and SID from conception to June 2023. Full-text case-control or cross-sectional studies were included in this study. Participants in the case group were children with ADHD aged 6-12 years. Review Manager Software (RevMan 5.4) was used for statistical analyses. Standardized mean differences (SMD) with 95% CIs were used to determine the differences between the two groups. Six studies were included in the present meta-analysis. They included 982 children, of whom, 204 were girls and 744 were boys. The mean age of the children was 8.86±2.03 years. The level of vitamin B was significantly different between children with and without ADHD [SMD -0.80, 95% CI (-1.55, -0.04)]. Vitamin B was significantly lower in children with ADHD [SMD -0.29, 95% CI (-0.42, -0.16)]. However, due to high heterogeneity (I = 93%), sensitivity analysis was used, I fell to 21%, and significant difference was observed between the two groups [SMD -0.19, 95% CI (-0.34, -0.04)]. The results of this systematic review showed that the level of vitamins B and B in children with ADHD was significantly lower than that in healthy children.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Vitamin B 12; Child; Female; Male; Pantothenic Acid; Cross-Sectional Studies; Case-Control Studies
PubMed: 38904980
DOI: 10.1024/0300-9831/a000809 -
Molecules (Basel, Switzerland) May 2024is a crucial edible fungus used in tea fermentation. In the industrial fermentation process, the fungus experiences a low to high osmotic pressure environment. To...
is a crucial edible fungus used in tea fermentation. In the industrial fermentation process, the fungus experiences a low to high osmotic pressure environment. To explore the law of material metabolism changes during osmotic pressure changes, NaCl was used here to construct different osmotic pressure environments. Liquid chromatography-mass spectrometry (LC-MS) combined with multivariate analysis was performed to analyze the distribution and composition of under different salt concentrations. At the same time, the in vitro antioxidant activity was evaluated. The LC-MS metabolomics analysis revealed significant differences between three mycelium samples grown on media with and without NaCl concentrations of 8% and 18%. The contents of gibberellin A3, A124, and prostaglandin A2 related to mycelial growth and those of arabitol and fructose-1,6-diphosphate related to osmotic pressure regulation were significantly reduced at high NaCl concentrations. The biosynthesis of energy-related pantothenol and pantothenic acid and antagonism-related fluvastatin, aflatoxin, and alternariol significantly increased at high NaCl concentrations. Several antioxidant capacities of mycelia were directly related to osmotic pressure and exhibited a significant downward trend with an increase in environmental osmotic pressure. The aforementioned results indicate that adapts to changes in salt concentration by adjusting their metabolite synthesis. At the same time, a unique set of strategies was developed to cope with high salt stress, including growth restriction, osmotic pressure balance, oxidative stress response, antioxidant defense, and survival competition.
Topics: Aspergillus; Metabolomics; Chromatography, Liquid; Salt Stress; Antioxidants; Metabolome; Osmotic Pressure; Mycelium; Mass Spectrometry; Sodium Chloride; Liquid Chromatography-Mass Spectrometry; Sugar Alcohols
PubMed: 38893389
DOI: 10.3390/molecules29112513 -
Nutrients Jun 2024Maintaining adequate hydration is critical to optimal health, well-being, and performance. Those who are physically active in stressful environments, such as warm and/or... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Maintaining adequate hydration is critical to optimal health, well-being, and performance. Those who are physically active in stressful environments, such as warm and/or humid scenarios, may be at particular risk for dehydration with ensuing loss of electrolytes, leading to sluggishness and impaired physical performance.
METHODS
We evaluated an electrolyte and amino acid product containing L-alanine and L-glutamine, as well as select vitamins [B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B12 (cobalamin), and vitamin C (ascorbic acid)]. Subjects ( = 40; four groups, = 10) were randomized to consume either a placebo packet or one, two, or three packets daily of the test product for 4 weeks with site visits at 0, 2, and 4 weeks. We tested safety and tolerability by analyzing hematological parameters (complete blood counts), metabolic parameters (hepatic, renal, acid-base balance), urinalysis end products, thyroid status [T3 (triiodothyronine), T4 (thyroxine), TSH (thyroid-stimulating hormone)], tolerability (via questionnaire), vital signs, and dietary intake.
RESULTS
Statistical analyses displayed ten significant main effects ( < 0.05) with white blood cells, lymphocytes, neutrophils, urinary pH, thyroxine, urination frequency, calcium, calories, fat, and cholesterol. Interactions for time and group ( < 0.05) were observed for MCV, eGFR, potassium, overall tolerability, bloating, and cramping-demonstrating mild GA disturbances. Little to no change of physiological relevance was noted for any outcome variable, regardless of dosing level.
CONCLUSIONS
Our results indicate the product was well-tolerated at all dosing levels and no significant adverse changes occurred in any of the test parameters compared to the placebo group, indicating relative safety of ingestion over a 4-week treatment period, at the volumes used, and outside the context of physical stress.
Topics: Humans; Female; Male; Adult; Amino Acids; Beverages; Young Adult; Dehydration; Double-Blind Method; Middle Aged; Electrolytes; Vitamins; Water-Electrolyte Balance
PubMed: 38892699
DOI: 10.3390/nu16111766 -
Nutrients May 2024This scoping review aims to investigate longitudinal changes in minerals and vitamins concentrations in human milk among the Chinese population. Following the PRISMA-ScR... (Review)
Review
This scoping review aims to investigate longitudinal changes in minerals and vitamins concentrations in human milk among the Chinese population. Following the PRISMA-ScR guidelines, a comprehensive and systematic literature search was conducted using both English and Chinese databases. Data were extracted and categorized into six defined lactation stages. We found that the concentration of most minerals decreased throughout the lactation period, although calcium (Ca) and magnesium (Mg) fluctuated slightly across lactation periods. Fat-soluble vitamins also showed a decline throughout the lactation period, while water-soluble vitamins exhibited an increasing trend. However, folic acid, biotin, and pantothenic acid demonstrated a downward trend. Overall, this review has identified the longitudinal changes in minerals and vitamins concentrations in human milk among the Chinese population. In order to conduct a more in-depth examination of maternal characteristics and nutritional factors of the composition of human milk, it is recommended to utilize standardized protocols for the collection and analysis of human milk samples.
Topics: Humans; Milk, Human; Female; Minerals; Vitamins; China; Lactation; Longitudinal Studies; Asian People; Adult; East Asian People
PubMed: 38892644
DOI: 10.3390/nu16111710 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2024To study the clinical and neurophysiological features of children with low cognitive tempo (NCT), as well as the effectiveness of the drug Pantogam in the treatment of...
OBJECTIVE
To study the clinical and neurophysiological features of children with low cognitive tempo (NCT), as well as the effectiveness of the drug Pantogam in the treatment of this pathology.
MATERIAL AND METHODS
A total of 90 children aged 8 to 10 years were examined. Of these, the main study group consisted of 30 children with NCT, the comparison group consisted of 30 children with a combined type of attention deficit hyperactivity disorder ADHD (ADHD-K), the control group consisted of 30 children without neuropsychiatric disorders. The study used clinical, neurophysiological (electroencephalography (EEG)) and parametric methods. The CMAS scale of apparent anxiety (The Children's Form of Manifest Anxiety Scale), the SNAP-IY scale (assessment of the degree of inattention, hyperactivity and impulsivity), the TOVA computer test (the Test of Variables of Attention), the scale «SCT» (Sluggish Cognitive Tempo) for assessing manifestations of low cognitive tempo, the «RAM» technique for quantifying working memory. Pantogam was used to treat patients at a dose of 750 mg per day for 8 weeks.
RESULTS
Patients with NCT are characterized by more pronounced attention disorders compared with healthy peers and with children with ADHD-K, and they have a decrease in mainly not selective attention, but the overall level of functional activity. Also, the group of children with NCT has an increased level of anxiety compared to the group of children with ADHD. A comparative analysis of the level of impulsivity showed that children with NCT are less characterized by a deficit in inhibition processes. According to the quantitative analysis of the EEG, specific changes in functional activity in the frontal and central regions of the cerebral cortex were revealed (a statistically significant increase in the ratio of absolute theta rhythm to beta1 rhythm, compared with other groups), reflecting insufficient cortical arousal and less focused neural states. When re-evaluating the condition of children with NCT after a course of therapy with Pantogam, an improvement in the form of a decrease in the degree of inattention, the severity of memory impairment and a decrease in reaction time was recorded in 60% of cases. According to quantitative EEG analysis, there was a significant decrease in the ratio of absolute theta rhythm to beta1 rhythm in the central leads of both hemispheres and in the parietal-temporal leads of the left hemisphere, indicating an increase in the level of overall activation of the cerebral cortex after a course of treatment.
CONCLUSION
Clinical and neurophysiological differences were revealed in patients with NCT and with combined ADHD. It has been shown that the use of Pantogam for the treatment of children with NCT leads not only to a decrease in the main manifestations of this disorder, but also to an improvement in the functional state of the brain.
Topics: Humans; Child; Attention Deficit Disorder with Hyperactivity; Male; Female; Electroencephalography; Pantothenic Acid; Cognition; Attention; Memory, Short-Term; gamma-Aminobutyric Acid
PubMed: 38884438
DOI: 10.17116/jnevro2024124051120 -
Biotechnic & Histochemistry : Official... Jun 2024Hypoxic-ischemic encephalopathy (HIE) is a cause of serious morbidity and mortality in newborns. Dexpanthenol, which is metabolized into D-pantothenic acid, has...
Hypoxic-ischemic encephalopathy (HIE) is a cause of serious morbidity and mortality in newborns. Dexpanthenol, which is metabolized into D-pantothenic acid, has antioxidant and other potentially therapeutic properties. We examined some effects of dexpanthenol on the brains of week-old rat pups with HIE induced by obstruction of the right carotid artery followed by keeping in 8% O for 2 hours. Dexpanthenol (500 mg/kg) was administered intraperitoneally to 16 of 32 pups with HIE. Protein, DNA, and lipid oxidation degradation products were assayed and hippocampal and cortical cell apoptosis and neuronal cell numbers were evaluated in stained sections. Dexpanthenol application reduced oxidative stress and inflammation. TNF-α and IL-6 cytokine levels in HIE also decreased with dexpanthenol treatment. The numbers of caspase-3 positive cells in the dentate gyrus and CA1/CA2/CA3 regions of the hippocampus was lower, and apoptosis was decreased in the dexpanthenol-treated animals. These findings suggest possible clinical applications of dexpanthenol in human HIE.
PubMed: 38869860
DOI: 10.1080/10520295.2024.2365231 -
Wei Sheng Yan Jiu = Journal of Hygiene... May 2024To establish an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of 11 nutritional components(thiamine,...
OBJECTIVE
To establish an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of 11 nutritional components(thiamine, riboflavin, nicotinamide, nicotinic acid, pantothenic acid, pyridoxine, pyridoxal, pyridoxamine, biotin, choline, L-carnitine) in liquid milk.
METHODS
Milk samples were shaken with 20 mmol/L ammonium formate solution and heated in a water bath at 100 ℃ for 30 min, then incubated with papain and acid phosphatase at 45 ℃ for 16 h, the lower liquid was collected after centrifugation for analysis. UPLC separation was performed on an ACQUITY~(TM) HSS T3(3.0 mm×150 mm, 1.8 μm) column, 2 mmol/L ammonium formate(containing 0.1% formic acid) solution and acetonitrile(containing 0.1% formic acid) were used as mobile phase. Quantitative detection was performed by internal standard method.
RESULTS
11 nutritional components can be effectively separated and detected in 12 min, and the linear correlation coefficients(R~2) were all above 0.995. The limits of detection(LODs) were between 0.05 and 0.50 μg/L, and the limits of quantification(LOQs) were between 0.20 and 1.25 μg/L. The recovery rates of three-level addition were 85.6%-119.3%, and the precision RSDs were between 3.68% and 7.82%(n=6). Based on the detection of 60 liquid milk samples from 5 different animals, it was found that the contents of 11 nutrients in liquid milk from different milk sources were significantly different, but pyridoxine could not be detected.
CONCLUSION
The method can quantitatively detect 11 water-soluble nutrients, including free and bound forms, by effective enzymolysis. It is sensitive, reproducible and can meet the needs of quantitative detection.
Topics: Milk; Tandem Mass Spectrometry; Animals; Chromatography, High Pressure Liquid; Niacinamide; Riboflavin; Nutrients; Pantothenic Acid; Cattle; Pyridoxine; Niacin; Carnitine
PubMed: 38839588
DOI: 10.19813/j.cnki.weishengyanjiu.2024.03.017