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Polymers Nov 2022Biomass rapid pyrolysis technology is easy to implement in continuous production and industrial application, and has become one of the leading technologies in the field...
Biomass rapid pyrolysis technology is easy to implement in continuous production and industrial application, and has become one of the leading technologies in the field of world renewable energy development. Agricultural and forestry waste is an important resource of renewable energy in China. In general, abandoned leaves in forest areas cause serious waste of resources. Its utilization may help to settle the problems of energy deficiency and environment pollution. In this study, Bunge leaves (A. Bunge) are used as the research object to study the pyrolysis and extract. The results showed that there are a lot of bioactive components in A. Bunge leaves extract, including acetamide, 5-hydroxymethylfurfural, R-limonene, d-mannose, and dihydroxyacetone. The active components of A. Bunge leaves supply scientific evidence for the exploration and exploitation of this plant. The pyrolysis products of A. Bunge leaves are rich in organic acids, aldehydes, and ketones, which means that A. Bunge leaves can be used as a crude material for the manufacturing of bio-oil or bio-fuel. The pyrolysis products include batilol, pregnenolone, benzoic acid, butyrolactone, and propanoic acid, which can be used in biological medicine, chemical crude materials, and industrial raw material reagents. Therefore, A. Bunge leaves can be used as a good crude material for bio-oil or biofuel production. Combining A. Bunge leaves and fast pyrolysis methods can effectively solve the problem of forestry and agricultural residues in the future.
PubMed: 36433130
DOI: 10.3390/polym14225003 -
Bioresources and Bioprocessing Nov 20221,3-Dihydroxyacetone (DHA) is a commercially important chemical and widely used in cosmetics, pharmaceuticals, and food industries as it prevents excessive water...
1,3-Dihydroxyacetone (DHA) is a commercially important chemical and widely used in cosmetics, pharmaceuticals, and food industries as it prevents excessive water evaporation, and provides anti-ultraviolet radiation protection and antioxidant activity. Currently, the industrial production of DHA is based on a biotechnological synthetic route using Gluconobacter oxydans. However, achieving higher production requires more improvements in the synthetic process. In this study, we compared DHA synthesis levels in five industrial wild-type Gluconobacter strains, after which the G. oxydans WSH-003 strain was selected. Then, 16 dehydrogenase genes, unrelated to DHA synthesis, were individually knocked out, with one strain significantly enhancing DHA production, reaching 89.49 g L and 42.27% higher than the wild-type strain. By optimizing the culture media, including seed culture and fermentation media, DHA production was further enhanced. Finally, using an established fed-batch fermentation system, DHA production reached 198.81 g L in a 5 L bioreactor, with a glycerol conversion rate of 82.84%.
PubMed: 38647819
DOI: 10.1186/s40643-022-00610-7 -
Current Research in Neurobiology 2022Triosephosphate isomerase deficiency (TPI Df) is a rare, aggressive genetic disease that typically affects young children and currently has no established treatment. TPI...
Triosephosphate isomerase deficiency (TPI Df) is a rare, aggressive genetic disease that typically affects young children and currently has no established treatment. TPI Df is characterized by hemolytic anemia, progressive neuromuscular degeneration, and a markedly reduced lifespan. The disease has predominately been studied using invertebrate and models, which lack key aspects of the human disease. While other groups have generated mammalian mutant strains, specifically with the mouse these do not recapitulate key characteristic phenotypes of the human disease. Reported here is the generation of a novel murine model of TPI Df. CRISPR-Cas9 was utilized to engineer the most common human disease-causing mutation, and mice were also isolated as a frame-shifting deletion. mice experience a markedly shortened lifespan, postural abnormalities consistent with extensive neuromuscular dysfunction, hemolytic anemia, pathological changes in spleen, and decreased body weight. There is a ∼95% reduction in TPI protein levels in animals compared to wild-type littermates, consistent with decreased TPI protein stability, a known cause of TPI Df. This work illustrates the capability of mice to serve as a mammalian model of human TPI Df. This work will allow for advancement in the study of TPI Df within a model with physiology similar to humans. The development of the model reported here will enable mechanistic studies of disease pathogenesis and, importantly, efficacy testing in a mammalian system for emerging TPI Df treatments.
PubMed: 36405628
DOI: 10.1016/j.crneur.2022.100062 -
Toxins Nov 2022The traditional Chinese herbal medicine Turcz. () has been widely adopted to treat nausea, diabetes, siriasis, and poor appetite. However, contains multiple...
The traditional Chinese herbal medicine Turcz. () has been widely adopted to treat nausea, diabetes, siriasis, and poor appetite. However, contains multiple pyrrolizidine alkaloids (PAs). This study aimed to investigate the hepatotoxicity of total alkaloids in (EFTAs) and identify the toxic mechanisms of EFTAs on hepatocytes. Liquid chromatography with a tandem mass spectrometry assay with reference standards indicated that EFTAs mainly consisted of eight PAs whose content accounted for 92.38% of EFTAs. EFTAs markedly decreased mouse body and liver weights and increased the contents of AST and ALT. The histopathological assays demonstrated that, after exposition to EFTAs, the structures of hepatocytes were damaged and the fibrosis and apoptosis in hepatocytes were accelerated. Moreover, EFTAs increased the serum level of inflammatory cytokines and aggravated circulating oxidative stress. A combination of hepatic proteomics and metabolomics was used to investigate the toxic mechanisms of EFTAs. The study revealed that EFTAs seriously disrupted glycerophospholipid metabolism by upregulating the contents of lysophosphatidylglycerol acyltransferase 1 and phosphatidylinositol and downregulating the contents of choline/ethanolamine kinase beta, choline-ethanolamine phosphotransferase 1, phospholipase D4, 1-acylglycerophosphocholine, phosphatidylcholine, and dihydroxyacetone phosphate in the liver, resulting in detrimental inflammation, fibrosis, and apoptosis. This study revealed that EFTAs induced severe hepatotoxicity by disrupting glycerophospholipid metabolism.
Topics: Mice; Animals; Eupatorium; Proteomics; Pyrrolizidine Alkaloids; Alkaloids; Metabolomics; Chemical and Drug Induced Liver Injury; Fibrosis; Glycerophospholipids; Choline
PubMed: 36356015
DOI: 10.3390/toxins14110765 -
RSC Advances Oct 2022In this work, the co-immobilization of formate dehydrogenase (FDH) and glycerol dehydrogenase (GlyDH) enzymes is proposed to reduce CO into formic acid, an important...
In this work, the co-immobilization of formate dehydrogenase (FDH) and glycerol dehydrogenase (GlyDH) enzymes is proposed to reduce CO into formic acid, an important chemical intermediate. The reduction of carbon dioxide is carried out by FDH to obtain formic acid, simultaneously, the GlyDH regenerated the nicotinamide cofactor in the reduced form (NADH) by the oxidation of glycerol into dihydroxyacetone. Natural zeolite was selected as immobilization support given its good properties and low cost. The natural zeolite was modified with subsequent acid-alkaline attacks to obtain a mesostructurization of the clinoptilolite. The two enzymes were co-immobilized on clinoptilolite, previously hetero-functionalized with amino and glyoxyl groups. The distribution of the enzymes was confirmed by fluorescence microscopy analysis. Furthermore, a great increase in the retained activity for the formate dehydrogenase enzyme was noted, passing from 18% to 89%, when the mesostructured clinoptilolite was used as support. The immobilization yield of formate dehydrogenase and glycerol dehydrogenase is around 100% with all the supports studied. The promising results suggest a possible development of this procedure in enzyme immobilization and biocatalysis. The biocatalysts were characterized to find the optimal pH and temperature. Furthermore, a thermal stability test at 50 °C was carried out on both enzymes, in free and immobilized forms. Finally, it was shown that the biocatalyst is effective in reducing CO, both by using the cofactor in the reduced form (NADH) or the oxidized form (NAD), obtaining NADH through the regeneration with glycerol in this latter case.
PubMed: 36349027
DOI: 10.1039/d2ra03459j -
Frontiers in Plant Science 2022The regulatory protein CP12 can bind glyceraldehyde 3-phosphate dehydrogenase (GapDH) and phosphoribulokinase (PRK) in oxygenic phototrophs, thereby switching on and off...
The regulatory protein CP12 can bind glyceraldehyde 3-phosphate dehydrogenase (GapDH) and phosphoribulokinase (PRK) in oxygenic phototrophs, thereby switching on and off the flux through the Calvin-Benson cycle (CBC) under light and dark conditions, respectively. However, it can be assumed that CP12 is also regulating CBC flux under further conditions associated with redox changes. To prove this hypothesis, the mutant Δ of the model cyanobacterium sp. PCC 6803 was compared to wild type and different complementation strains. Fluorescence microscopy showed for the first time the kinetics of assembly and disassembly of the CP12-GapDH-PRK complex, which was absent in the mutant Δ. Metabolome analysis revealed differences in the contents of ribulose 1,5-bisphosphate and dihydroxyacetone phosphate, the products of the CP12-regulated enzymes GapDH and PRK, between wild type and mutant Δ under changing CO conditions. Growth of Δ was not affected at constant light under different inorganic carbon conditions, however, the addition of glucose inhibited growth in darkness as well as under diurnal conditions. The growth defect in the presence of glucose is associated with the inability of Δ to utilize external glucose. These phenotypes could be complemented by ectopic expression of the native CP12 protein, however, expression of CP12 variants with missing redox-sensitive cysteine pairs only partly restored the growth with glucose. These experiments indicated that the loss of GapDH-inhibition CP12 is more critical than PRK association. Measurements of the NAD(P)H oxidation revealed an impairment of light intensity-dependent redox state regulation in Δ Collectively, our results indicate that CP12-dependent regulation of the CBC is crucial for metabolic adjustment under conditions leading to redox changes such as diurnal conditions, glucose addition, and different CO conditions in cyanobacteria.
PubMed: 36330266
DOI: 10.3389/fpls.2022.1028794 -
Scientific Reports Oct 2022In vitro and in vivo studies have established the organic anion transporters OAT1 (SLC22A6, NKT) and OAT3 (SLC22A8) among the main multi-specific "drug" transporters....
In vitro and in vivo studies have established the organic anion transporters OAT1 (SLC22A6, NKT) and OAT3 (SLC22A8) among the main multi-specific "drug" transporters. They also transport numerous endogenous metabolites, raising the possibility of drug-metabolite interactions (DMI). To help understand the role of these drug transporters on metabolism across scales ranging from organ systems to organelles, a formal multi-scale analysis was performed. Metabolic network reconstructions of the omics-alterations resulting from Oat1 and Oat3 gene knockouts revealed links between the microbiome and human metabolism including reactions involving small organic molecules such as dihydroxyacetone, alanine, xanthine, and p-cresol-key metabolites in independent pathways. Interestingly, pairwise organ-organ interactions were also disrupted in the two Oat knockouts, with altered liver, intestine, microbiome, and skin-related metabolism. Compared to older models focused on the "one transporter-one organ" concept, these more sophisticated reconstructions, combined with integration of a multi-microbial model and more comprehensive metabolomics data for the two transporters, provide a considerably more complex picture of how renal "drug" transporters regulate metabolism across the organelle (e.g. endoplasmic reticulum, Golgi, peroxisome), cellular, organ, inter-organ, and inter-organismal scales. The results suggest that drugs interacting with OAT1 and OAT3 can have far reaching consequences on metabolism in organs (e.g. skin) beyond the kidney. Consistent with the Remote Sensing and Signaling Theory (RSST), the analysis demonstrates how transporter-dependent metabolic signals mediate organ crosstalk (e.g., gut-liver-kidney) and inter-organismal communication (e.g., gut microbiome-host).
Topics: Humans; Gastrointestinal Microbiome; Metabolic Networks and Pathways; Metabolomics; Organic Anion Transport Protein 1; Organic Anion Transporters, Sodium-Independent
PubMed: 36316339
DOI: 10.1038/s41598-022-21091-w -
Molecular Metabolism Dec 2022Glycerol-3-phosphate (Gro3P) phosphatase (G3PP) hydrolyzes Gro3P to glycerol that exits the cell, thereby operating a "glycerol shunt", a metabolic pathway that we...
OBJECTIVE
Glycerol-3-phosphate (Gro3P) phosphatase (G3PP) hydrolyzes Gro3P to glycerol that exits the cell, thereby operating a "glycerol shunt", a metabolic pathway that we identified recently in mammalian cells. We have investigated the role of G3PP and the glycerol shunt in the regulation of glucose metabolism and lipogenesis in mouse liver.
METHODS
We generated hepatocyte-specific G3PP-KO mice (LKO), by injecting AAV8-TBG-iCre to male G3PP mice. Controls received AAV8-TBG-eGFP. Both groups were fed chow diet for 10 weeks. Hyperglycemia (16-20 mM) was induced by glucose infusion for 55 h. Hepatocytes were isolated from normoglycemic mice for ex vivo studies and targeted metabolomics were measured in mice liver after glucose infusion.
RESULTS
LKO mice showed no change in body weight, food intake, fed and fasted glycemia but had increased fed plasma triglycerides. Hepatic glucose production from glycerol was increased in fasted LKO mice. LKO mouse hepatocytes displayed reduced glycerol production, elevated triglyceride and lactate production at high glucose concentration. Hyperglycemia in LKO mice led to increased liver weight and accumulation of triglycerides, glycogen and cholesterol together with elevated levels of Gro3P, dihydroxyacetone phosphate, acetyl-CoA and some Krebs cycle intermediates in liver. Hyperglycemic LKO mouse liver showed elevated expression of proinflammatory cytokines and M1-macrophage markers accompanied by increased plasma triglycerides, LDL/VLDL, urea and uric acid and myocardial triglycerides.
CONCLUSIONS
The glycerol shunt orchestrated by G3PP acts as a glucose excess detoxification pathway in hepatocytes by preventing metabolic disturbances that contribute to enhanced liver fat, glycogen storage, inflammation and lipid build-up in the heart. We propose G3PP as a novel therapeutic target for hepatic disorders linked to nutrient excess.
Topics: Animals; Male; Mice; Glucose; Glycerol; Glycogen; Hyperglycemia; Liver; Phosphoric Monoester Hydrolases; Triglycerides
PubMed: 36198384
DOI: 10.1016/j.molmet.2022.101609 -
Nature Communications Oct 2022Many biomass intermediates are polyols and selectively oxidizing only a primary or secondary alcohol group is beneficial for the valorization of these intermediates. For...
Many biomass intermediates are polyols and selectively oxidizing only a primary or secondary alcohol group is beneficial for the valorization of these intermediates. For example, production of 1,3-dihydroxyacetone, a highly valuable oxidation product of glycerol, requires selective secondary alcohol oxidation. However, selective secondary alcohol oxidation is challenging due to its steric disadvantage. This study demonstrates that NiOOH, which oxidizes alcohols via two dehydrogenation mechanisms, hydrogen atom transfer and hydride transfer, can convert glycerol to 1,3-dihydroxyacetone with high selectivity when the conditions are controlled to promote hydrogen atom transfer, favoring secondary alcohol oxidation. This rational production of 1,3-dihydroxyacetone achieved by selectively enabling one desired dehydrogenation pathway, without requiring alteration of catalyst composition, demonstrates how comprehensive mechanistic understanding can enable predictive control over selectivity.
Topics: Catalysis; Dihydroxyacetone; Ethanol; Glycerol; Hydrogen
PubMed: 36195626
DOI: 10.1038/s41467-022-33637-7 -
Journal of Oral Microbiology 2022The etiology of dental caries remains poorly understood. With the advent of next-generation sequencing, a number of studies have focused on the microbial ecology of the...
BACKGROUND
The etiology of dental caries remains poorly understood. With the advent of next-generation sequencing, a number of studies have focused on the microbial ecology of the disease. However, taxonomic associations with caries have not been consistent. Researchers have also pursued function-centric studies of the caries microbial communities aiming to identify consistently conserved functional pathways. A major question is whether changes in microbiome are a cause or a consequence of the disease. Thus, there is a critical need to define conserved functional signatures at the onset of dental caries.
METHODS
Since it is unethical to induce carious lesions clinically, we developed an innovative longitudinal model integrated with the advanced non-invasive multiphoton second harmonic generation bioimaging to spot the very early signs of dental caries, combined with 16S rRNA short amplicon sequencing and liquid chromatography-mass spectrometry-based targeted metabolomics.
FINDINGS
For the first time, we induced longitudinally monitored caries lesions validated with the scanning electron microscope. Consequently, we spotted the caries onset and, associated with it, distinguished five differentiating metabolites - Lactate, Pyruvate, Dihydroxyacetone phosphate, Glyceraldehyde 3-phosphate (upregulated) and Fumarate (downregulated). Those metabolites co-occurred with certain bacterial taxa; , and , regardless of the abundance of other taxa.
INTERPRETATION
These findings are crucial for understanding the etiology and dynamics of dental caries, and devising targeted interventions to prevent disease progression.
PubMed: 36189437
DOI: 10.1080/20002297.2022.2123624