Accumulation Of Fatty Acids Research Articles

Organic chromium derived from the chelation of Ganoderma lucidum polysaccharide and chromium (III) alleviates metabolic syndromes and intestinal microbiota dysbiosis induced by high-fat and high-fructose diet

Organic chromium is of great interest and has become an important chromium supplement resource in recent years because of its low toxicity and easy absorption. In our previous study, we synthesized a novel organic chromium [GLP-Cr] through the chelation of Ganoderma lucidum polysaccharide and chromium (III). The purpose of this study was to investigate the beneficial effects of GLP-Cr on the improvement of metabolic syndromes (MetS) in mice fed with a high-fat and high-fructose diet (HFHFD) and its mechanism of action. The results indicated that oral administration of GLP-Cr inhibited the excessive exaltation of body weight, glucose tolerance, fasting blood glucose and lipid levels, hepatic total cholesterol (TC), triglyceride (TG) levels caused by HFHFD. Besides, 16S rRNA amplicon sequencing showed that GLP-Cr intervention evidently ameliorated intestinal microbiota dysbiosis by changing the proportions of some intestinal microbial phylotypes. In addition, correlation network-based analysis indicated that the key intestinal microbial phylotypes were closely related to biochemical parameters associated with MetS under GLP-Cr intervention. Liver metabolomics analysis suggested that GLP-Cr intervention significantly regulated the levels of some biomarkers involved in alpha-linolenic acid metabolism, fatty acid biosynthesis, steroid hormone biosynthesis, glycerophospholipid metabolism, glycerolipid metabolism, steroid hormone biosynthesis, primary bile acid biosynthesis, and so on. Moreover, GLP-Cr intervention regulated liver mRNA levels of key genes associated with glucose and lipid metabolism. The mRNA level of glucose transporter type 4 (Glut4) was markedly increased by GLP-Cr intervention, and the mRNA levels of phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6Pase) in the liver were significantly decreased. Meanwhile, GLP-Cr intervention significantly decreased hepatic mRNA levels of cluster of differentiation 36 (Cd36), acetyl-CoA carboxylase 1 (Acc1) and sterol regulatory element binding protein-1c (Srebp-1c), indicating that GLP-Cr intervention inhibited the excessive accumulation of free fatty acids in the liver. These findings suggest that the prevention of hyperglycemia and dyslipidemia by GLP-Cr may be closely related to the regulation of gut microbial composition and hepatic metabolic pathways, thus GLP-Cr can be serving as a functional component in the prevention of MetS.

Insight into effects of polyethylene microplastics in anaerobic digestion systems of waste activated sludge: Interactions of digestion performance, microbial communities and antibiotic resistance genes

The environmental risks of microplastics (MPs) have raised an increasing concern. However, the effects of MPs in anaerobic digestion (AD) systems of waste activated sludge (WAS), especially on the fate of antibiotic resistance genes (ARGs), have not been clearly understood. Herein, the variation and interaction of digestion performance, microbial communities and ARGs during AD process of WAS in the presence of polyethylene (PE) MPs with two sizes, PE MPs-180μm and PE MPs-1mm, were investigated. The results showed that the presence of PE MPs, especially PE MPs-1mm, led to the increased hydrolysis of soluble polysaccharides and proteins and the accumulation of volatile fatty acids. The methane production decreased by 6.1% and 13.8% in the presence of PE MPs-180μm and PE MPs-1mm, respectively. Together with this process, hydrolytic bacteria and acidogens were enriched, and methanogens participating in acetoclastic methanogenesis were reduced. Meanwhile, ARGs were enriched obviously by the presence of PE MPs, the abundances of which in PE MPs-180μm and PE MPs-1mm groups were 1.2–3.0 times and 1.5–4.0 times higher than that in the control by the end of AD. That was associated with different co-occurrence patterns between ARGs and bacterial taxa and the enrichment of ARG-hosting bacteria caused by the presence of PE MPs. Together these results suggested the adverse effects of PE MPs on performance and ARGs removal during AD process of WAS through inducing the changes of microbial populations.

Melatonin maintained higher contents of unsaturated fatty acid and cell membrane structure integrity in banana peel and alleviated postharvest chilling injury

Exogenous melatonin confers the chilling tolerance of banana fruit by promoting reactive oxygen species (ROS) scavenging system and inducing the unsaturated fatty acid synthesis. The results showed that melatonin treatment increased the contents of phospholipids, promoted the ROS scavenging enzyme, and restrained the activities of lipoxygenase (LOX), and thus reduced the lipid peroxidation of banana peel. In addition, melatonin treatment increased the flavonoids and proline contents, which was conducive to antioxidant capacity. Interestingly, the enhanced antioxidant capacity is conducive to the stability of unsaturated fatty acids and reduce the enzymatic browning reaction. Moreover, melatonin treatment induced the expression of omega-3/6 fatty acid desaturase and triggered the fatty acid metabolism activity, by which maintained higher contents of unsaturated fatty acid in banana peel. Moreover, melatonin treatment stimulated the accumulation of fatty acids in banana peel, and was involved in alleviating fruit chilling injury.

Carbohydrate Repartitioning in the Rice Starch Branching Enzyme IIb Mutant Stimulates Higher Resistant Starch Content and Lower Seed Weight Revealed by Multiomics Analysis.

The starch branching enzyme IIb mutant (be2b) in rice significantly increases the resistant starch (RS) content and leads to reduced seed weight. However, the underlying metabolic mechanisms remain unclear. Proteomic analysis indicated that upregulation of starch synthase IIa (SSIIa) and SSIIIa and downregulation of BEI and SSI were possibly responsible for the decreased short amylopectin chains (DP 6-15) and increased longer chains (DP > 16) of be2b starch. The upregulation of granule-bound starch synthase led to increased amylose content (AC). These changes in the amylopectin structure and AC accounted for the increased RS content. α-Amylase 2A showed the strongest upregulation (up to 8.45-fold), indicating that the loss of BEIIb activity enhanced starch degradation. Upregulation of glycolysis-related proteins stimulated carbohydrate repartitioning through glycerate-3-phosphate and promoted the accumulation of tricarboxylic acid cycle intermediates, amino acids, and fatty acids. The unexpected carbohydrate partitioning and enhanced starch degradation resulted in the reduced seed weight in the be2b mutant.

Transcriptome changes in stages of non-alcoholic fatty liver disease.

BACKGROUNDNon-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States and globally. The currently understood model of pathogenesis consists of a ‘multiple hit’ hypothesis in which environmental and genetic factors contribute to hepatic inflammation and injury. AIMTo examine the genetic expression of NAFLD and non-alcoholic steatohepatitis (NASH) tissue samples to identify common pathways that contribute to NAFLD and NASH pathogenesis.METHODSWe employed the Search Tag Analyze Resource for Gene Expression Omnibus platform to search the The National Center for Biotechnology Information Gene Expression Omnibus to elucidate NAFLD and NASH pathology. For NAFLD, we conducted meta-analysis of data from 58 NAFLD liver biopsies and 60 healthy liver biopsies; for NASH, we analyzed 187 NASH liver biopsies and 154 healthy liver biopsies. RESULTSOur results from the NAFLD analysis reinforce the role of altered metabolism, inflammation, and cell survival in pathogenesis and support recently described contributors to disease activity, such as altered androgen and long non-coding RNA activity. The top upstream regulator was found to be sterol regulatory element binding transcription factor 1 (SREBF1), a transcription factor involved in lipid homeostasis. Downstream of SREBF1, we observed upregulation in CXCL10, HMGCR, HMGCS1, fatty acid binding protein 5, paternally expressed imprinted gene 10, and downregulation of sex hormone-binding globulin and insulin-like growth factor 1. These molecular changes reflect low-grade inflammation secondary to accumulation of fatty acids in the liver. Our results from the NASH analysis emphasized the role of cholesterol in pathogenesis. Top canonical pathways, disease networks, and disease functions were related to cholesterol synthesis, lipid metabolism, adipogenesis, and metabolic disease. Top upstream regulators included pro-inflammatory cytokines tumor necrosis factor and IL1B, PDGF BB, and beta-estradiol. Inhibition of beta-estradiol was shown to be related to derangement of several cellular downstream processes including metabolism, extracellular matrix deposition, and tumor suppression. Lastly, we found riciribine (an AKT inhibitor) and ZSTK-474 (a PI3K inhibitor) as potential drugs that targeted the differential gene expression in our dataset. CONCLUSIONIn this study we describe several molecular processes that may correlate with NAFLD disease and progression. We also identified ricirbine and ZSTK-474 as potential therapy.

Innate Immune Training of Human Macrophages by Cathelicidin Analogs.

Trained innate immunity can be induced in human macrophages by microbial ligands, but it is unknown if exposure to endogenous alarmins such as cathelicidins can have similar effects. Previously, we demonstrated sustained protection against infection by the chicken cathelicidin-2 analog DCATH-2. Thus, we assessed the capacity of cathelicidins to induce trained immunity. PMA-differentiated THP-1 (dTHP1) cells were trained with cathelicidin analogs for 24 hours and restimulated after a 3-day rest period. DCATH-2 training of dTHP-1 cells amplified their proinflammatory cytokine response when restimulated with TLR2/4 agonists. Trained cells displayed a biased cellular metabolism towards mTOR-dependent aerobic glycolysis and long-chain fatty acid accumulation and augmented microbicidal activity. DCATH-2-induced trained immunity was inhibited by histone acetylase inhibitors, suggesting epigenetic regulation, and depended on caveolae/lipid raft-mediated uptake, MAPK p38 and purinergic signaling. To our knowledge, this is the first report of trained immunity by host defense peptides.

Chronic effects of benzalkonium chlorides on short chain fatty acids and methane production in semi-continuous anaerobic digestion of waste activated sludge

As an emerging pollutant, benzalkonium chlorides (BACs) potentially enriched in waste activated sludge (WAS). However, the microbial response mechanism under chronic effects of BACs on acidogenesis and methanogenesis in anaerobic digestion (AD) has not been clearly disclosed. This study investigated the AD (by-)products and microbial evolution under low to high BACs concentrations from bioreactor startup to steady running. It was found that BACs can lead to an increase of WAS hydrolysis and fermentation, but a disturbance to acidogenic bacteria also occurred at low BACs concentration. A noticeable inhibition to methanogenesis occurred when BAC concentration was up to 15 mg/g TSS. Metagenomic analysis revealed the key genes involved in acetic acid (HAc) biosynthesis (i.e. phosphate acetyltransferase, PTA), β-oxidation pathway (acetyl-CoA C-acetyltransferase) and propionic acid (HPr) conversion was slightly promoted compared with control. Furthermore, BACs inhibited the acetotrophic methanogenesis (i.e. acetyl-CoA synthetase), especially BAC concentration was up to 15 mg/g TSS, thereby enhanced short chain fatty acids (SCFAs) accumulation. Overall, chronic stimulation of functional microorganisms with increasing concentrations of BACs impact WAS fermentation.

Multivariate insights into enhanced biogas production in thermophilic dry anaerobic co-digestion of food waste with kitchen waste or garden waste: Process properties, microbial communities and metagenomic analyses

Multisubstrate synergetic anaerobic co-digestion can effectively overcome low efficiency of food waste (FW) mono-digestion. This study investigated the effect of supplementing FW with kitchen waste (KW) or garden waste (GW) on thermophilic dry anaerobic co-digestion. FW-KW and FW-GW co-digestion enhanced biogas production by 24.69 % and 44.96 % at organic loading rate (OLR) of 3 g VS L-1 d-1, and increased OLR tolerance from 3 to 4 g VS L-1 d-1 through mitigating ammonia nitrogen inhibition and volatile fatty acids accumulation. Co-digestion enriched the dominant hydrolytic bacteria Defluviitoga, resulting in an acceleration of substrate hydrolysis. FW-KW co-digestion improved biogas production by increasing gene abundance related to key enzymes in methanogenesis pathways and promoting the conversion of intermediate products into methane. FW-GW co-digestion enhanced biogas production by enriching ABC transporters-associated genes, leading to efficient substrate utilization. This study provides a promising approach for FW treatment with multivariate insights into thermophilic dry anaerobic co-digestion.

Mechanism of dielectric barrier discharge plasma technology to improve the quantity of short-chain fatty acids in anaerobic fermentation of waste active sludge.

The mechanism of improving the anaerobic fermentation performance of waste active sludge by using dielectric barrier discharge (DBD) plasma pretreatment technology was investigated. The maximum accumulation of short-chain fatty acids (SCFAs) was observed on the 7th day of anaerobic fermentation when the DBD power was 76.50 W, which was 1726.70 mg COD/L, 1.50 times of the control group. The ratio of acetic acid in DBD group was 9.30% higher than that in the control. Further mechanism research indicated that DBD pretreatment can destroy the structure of extracellular polymer substances and release organic substances such as protein and polysaccharide. The dissolved organic matter analysis indicated that the DBD technique could increase the release of biodegradable organics (eg., tyrosine proteins, soluble microbial by-products), thus accelerate the biotransformation of organic substance. Bacterial community structure analysis showed that the increase in the abundance of Firmicutes and Bacteroidetes and the decrease in the abundance of Proteobacteria in DBD group were beneficial to the accumulation of SCFAs. Besides, further archaeal analysis indicated that the decrease of Methanosaeta sp. and Methanosarcina sp. abundance in the DBD group facilitate acetic acid accumulation. This study demonstrated that the DBD technique can be used as an effective and potential pretreatment method to improve sludge anaerobic fermentation performance.

Complex network analysis of slaughterhouse waste anaerobic digestion: From failure to success of long-term operation

The study explored slaughterhouse waste (SHW) as prime feedstock associated with and without supplement of an external slowly degradable lignocellulosic carbon source to overcome the synergistic co-inhibitions of ammonia and fatty acids. Long-term solid-state digestion (SSD) and liquid-state digestion (LSD) were investigated using a mixture of pork liver and fat. At 2.0 g volatile solids (VS) L−1 d−1 of organic loading rate (OLR), the two reactors of SSD experienced operational instability due to ammonia inhibition and volatile fatty acid (VFA) accumulation while LSD successfully produced 0.725 CH4 L CH4 g−1VS during 197 d of working days under unfavorable condition with high total ammonia nitrogen (>4.7 g/L) and VFAs concentration (>1.9 g/L). The network analysis between complex microflora and operational parameters provided an insight for sustainable biogas production using SHW. Among all, hydrogenotrophic methanogens have shown better resistance than acetoclastic methanogens.

Peruraian Anaerobik Termofilik Palm Oil Mill Effluent dengan Variasi Konsentrasi Substrat

High utilization of palm oil in Indonesia corresponds to palm oil mill effluent (POME). The POME has chemical oxygen demand (COD) of up to 100.000 mg/L, which can pollute the ecosystem if not adequately treated. One of the methods to manage POME is anaerobic thermophilic digestion. The advantage of this method is the production of methane gas which is a form of alternative energy. Substrate concentration affects anaerobic digestion. This preliminary experiment aims to evaluate the performance of anaerobic thermophilic digestion on various POME concentrations at 55 °C. The anaerobic digestion was run with 16.000, 11.000 and 5.000 mg sCOD/L substrate concentrations. Digested cow manure (DCM) was used as inoculum. The process was running in a continuous system after 7-days of acclimatization of the batch system. The result shows that 16.000 and 11.000 mg sCOD/L concentrations produced more methane, but the methane yield was not statistically significant with the Tukey test (p=0,05). The POME with a 5.000 mg sCOD/L concentration produced less methane and plummeted after day 85. The lower methane production at lower substrate concentration was due to the low sCOD availability and high volatile fatty acid (VFA) accumulation which inhibited the methane production.

Vitamin C attenuates predisposition to high-fat diet-induced metabolic dysregulation in GLUT10-deficient mouse model

BackgroundThe development of type 2 diabetes mellitus (T2DM) is highly influenced by complex interactions between genetic and environmental (dietary and lifestyle) factors. While vitamin C (ascorbic acid, AA) has been suggested as a complementary nutritional treatment for T2DM, evidence for the significance and beneficial effects of AA in T2DM is thus far inconclusive. We suspect that clinical studies on the topic might need to account for combination of genetic and dietary factors that could influence AA effects on metabolism. In this study, we tested this general idea using a mouse model with genetic predisposition to diet-induced metabolic dysfunction. In particular, we utilized mice carrying a human orthologous GLUT10G128E variant (GLUT10G128E mice), which are highly sensitive to high-fat diet (HFD)-induced metabolic dysregulation. The genetic variant has high relevance to human populations, as genetic polymorphisms in glucose transporter 10 (GLUT10) are associated with a T2DM intermediate phenotype in nondiabetic population.ResultsWe investigated the impacts of AA supplementation on metabolism in wild-type (WT) mice and GLUT10G128E mice fed with a normal diet or HFD. Overall, the beneficial effects of AA on metabolism were greater in HFD-fed GLUT10G128E mice than in HFD-fed WT mice. At early postnatal stages, AA improved the development of compromised epididymal white adipose tissue (eWAT) in GLUT10G128E mice. In adult animals, AA supplementation attenuated the predisposition of GLUT10G128E mice to HFD-triggered eWAT inflammation, adipokine dysregulation, ectopic fatty acid accumulation, metabolic dysregulation, and body weight gain, as compared with WT mice.ConclusionsTaken together, our findings suggest that AA has greater beneficial effects on metabolism in HFD-fed GLUT10G128E mice than HFD-fed WT mice. As such, AA plays an important role in supporting eWAT development and attenuating HFD-induced metabolic dysregulation in GLUT10G128E mice. Our results suggest that proper WAT development is essential for metabolic regulation later in life. Furthermore, when considering the usage of AA as a complementary nutrition for prevention and treatment of T2DM, individual differences in genetics and dietary patterns should be taken into account.

Metabolomic Analysis of Human Astrocytes in Lipotoxic Condition: Potential Biomarker Identification by Machine Learning Modeling.

The association between neurodegenerative diseases (NDs) and obesity has been well studied in recent years. Obesity is a syndrome of multifactorial etiology characterized by an excessive accumulation and release of fatty acids (FA) in adipose and non-adipose tissue. An excess of FA generates a metabolic condition known as lipotoxicity, which triggers pathological cellular and molecular responses, causing dysregulation of homeostasis and a decrease in cell viability. This condition is a hallmark of NDs, and astrocytes are particularly sensitive to it, given their crucial role in energy production and oxidative stress management in the brain. However, analyzing cellular mechanisms associated with these conditions represents a challenge. In this regard, metabolomics is an approach that allows biochemical analysis from the comprehensive perspective of cell physiology. This technique allows cellular metabolic profiles to be determined in different biological contexts, such as those of NDs and specific metabolic insults, including lipotoxicity. Since data provided by metabolomics can be complex and difficult to interpret, alternative data analysis techniques such as machine learning (ML) have grown exponentially in areas related to omics data. Here, we developed an ML model yielding a 93% area under the receiving operating characteristic (ROC) curve, with sensibility and specificity values of 80% and 93%, respectively. This study aimed to analyze the metabolomic profiles of human astrocytes under lipotoxic conditions to provide powerful insights, such as potential biomarkers for scenarios of lipotoxicity induced by palmitic acid (PA). In this work, we propose that dysregulation in seleno-amino acid metabolism, urea cycle, and glutamate metabolism pathways are major triggers in astrocyte lipotoxic scenarios, while increased metabolites such as alanine, adenosine, and glutamate are suggested as potential biomarkers, which, to our knowledge, have not been identified in human astrocytes and are proposed as candidates for further research and validation.

Food potential of Scenedesmus obliquus biomasses obtained from photosynthetic cultivations associated with carbon dioxide mitigation

Microalgae are photosynthetic microorganisms that stand out from conventional food sources and ingredients due to their high growth rate and adaptability. In addition to being highly sustainable, significant concentrations of proteins, lipids, and pigments accumulate in their cell structures from photosynthesis. Hence, this study sought to evaluate the food potential of Scenedesmus obliquus biomasses obtained from photosynthetic cultures enriched with 3, 5, 10, 15, 20, and 25% carbon dioxide (CO2) (v/v). Cultivations with 3, 5, and 10% CO2 showed greater amino acids and proteins synthesis; the protein content reached values above 56% of the dry biomass and high protein quality, due to the presence of most essential amino acids at recommended levels for the human diet. The highest concentrations of chlorophylls were found in cultures with 15, 20, and 25% CO2 (24.2, 23.1 and 30.8 mg g−1, respectively), although the profiles showed higher percentages of degradation compounds. Carotenoid concentrations were three times higher in cultures with 3, 5, and 10% CO2 (25.3, 22.7 and 18.1 mg g−1, respectively) and all-trans-β-carotene was the major compound. Lipid synthesis was intensified at higher CO2 enrichment; the percentages obtained were 14.8% of lipids in the culture with 15% CO2, 15.0% with 20% CO2, and 13.7% with 25% CO2. In addition, greater polyunsaturated fatty acids accumulation and a significant reduction in the n6/n3 ratio were also observed at the highest CO2 concentrations. Our findings showed that CO2 treatments significantly altered all compounds concentrations in S. obliquus biomasses, which presented satisfactory composition for application in foods and as ingredients.

Genetic and Biochemical Investigation of Seed Fatty Acid Accumulation in Arabidopsis.

As a vegetable oil, consisting principally of triacylglycerols, is the major storage form of photosynthetically-fixed carbon in oilseeds which are of significant agricultural and industrial value. Photosynthesis in chlorophyll-containing green seeds, along with photosynthesis in leaves and other green organs, generates ATP and reductant (NADPH and NADH) needed for seed fatty acid production. However, contribution of seed photosynthesis to fatty acid accumulation in seeds have not been well-defined. Here, we report the contribution of seed-photosynthesis to fatty acid production by probing segregating green (photosynthetically-competent) and non-green or yellow (photosynthetically-non-competent) seeds in siliques of an Arabidopsis chlorophyll synthase mutant. Using this mutant, we found that yellow seeds lacking photosynthetic capacity reached 80% of amounts of oil in green seeds at maturity. Combining this with studies using shaded siliques, we determined that seed-photosynthesis accounts for 20% and silique and leaf/stem photosynthesis each account for ~40% of the ATP and reductant for seed oil production. Transmission electron microscopy (TEM) and pyridine nucleotides and ATP analyses revealed that seed photosynthesis provides ATP and reductant for oil production mostly during early development, as evidenced by delayed oil accumulation in non-green seeds. Transcriptomic analyses suggests that the oxidative pentose phosphate pathway could be the source of carbon, energy and reductants required for fatty acid synthesis beyond the early stages of seed development.

Investigation of the Molecular Mechanisms Underlying the Antiatherogenic Actions of Kaempferol in Human THP-1 Macrophages.

Cardiovascular disease (CVD) is causing high mortality worldwide (World Health Organization-WHO, 2015). Atherosclerosis, the hardening and narrowing of arteries caused by the accumulation of fatty acids and lipids (cholesterol plaques), is a main reason of stroke, myocardial infarction, and angina. Present therapies for cardiovascular disease basically use statins such as β-Hydroxy β-methylglutaryl-CoA, with <70% efficacy and multiple side effects. An in vitro investigation was conducted to evaluate the impact of kaempferol, a natural medication, in an atherosclerotic cell model. We used cytotoxicity assays, Boyden chamber invasion assays, and quantitative PCR. Affymetrix microarrays were used to profile the entire transcriptome of kaempferol-treated cell lines, and Partek Genomic Suite was used to interpret the results. Kaempferol was not cytotoxic to THP-1 macrophages. In comparison to the control, kaempferol reduced monocyte migration mediated by monocyte chemotactic protein 1 (MCP-1) by 80%. The qPCR results showed a 73.7-fold reduction in MCP-1 and a 2.5-fold reduction in intercellular adhesion molecule 1 (ICAM-1) expression in kaempferol-treated cells. In interferon gamma (IFN-γ) without kaempferol and IFN-γ with kaempferol treated cells, we found 295 and 168 differentially expressed genes (DEGs), respectively. According to DEG pathway analysis, kaempferol exhibits anti-atherosclerosis and anti-inflammatory characteristics. Kaempferol is an effective and safe therapy for atherosclerosis.

Multi-advantageous sorghum as feedstock for biogas production: A comparison between single-stage and two-stage anaerobic digestion systems.

Anaerobic digestion (AD) is a keystone in the circular economy concept . The produced biogas can be demand-driven controlled and regionally adaptable, but sustainable feedstocks are required. Sorghum is a valuable alternative considering its bioenergy potential and wide adaptability to different environmental conditions. In this study, AD of sorghum silage was performed in a single-stage continuously stirred tank reactor (CSTR) and in a two-stage leach-bed reactor (LBR) system. The two-stage LBR system revealed higher methane yields (434 L N kg VS −1 ) compared to the single-stage CSTR (308 L N kg VS −1 ). Methane content of biogas ranged from 53 to 59% in both systems. Only the CSTR exhibited acids accumulation, led by propionic acid concentration (2.0 g L −1 ). Buffer capacity of the two-stage LBR system was superior to the CSTR. Technical disruptions and constant ammonium content declination were shown in both systems, associated to inherent characteristics of fibrous sorghum. AD of sorghum biomass, however, can be effectively performed under controlled conditions, generating high methane yields in both types of systems. • Mesophilic AD of fibrous sorghum in a single- and in a two-stage digestion system. • Accumulation of volatile fatty acids occurred during experiments in CSTR. • Two-stage system produced higher methane yields and showed better process stability. • A constant declination of the ammonium-nitrogen content was observed. • Fibrous sorghum caused technical disruption in both types of system.

Influence pathway of iron ions with different valences for methane fermentation of vegetable waste

Anaerobic digestion (AD) is a promising approach for vegetable waste (VW) recycling and energy recovery but methanogenesis is always inhibited by acid accumulation. The addition of a mixture of iron and other elements has proved effective on reducing acid inhibition during AD of VW, but the effect of use of iron alone has rarely been assessed. In the present study, we compared the effects of Fe0 and Fe2+ on methane fermentation from VW at an organic loading rate of 1.5 gVS/L/d. The results indicated that Fe0 maintained a pH &amp;gt; 7.7, oxidation reduction potential &amp;lt;−520, and methane production rate (MPR) at 250–300 mL/gVS/d. Partial least squares path modeling and correlation analysis revealed Fe0 maintained pH for high MPR mainly through enhancing the conversion of propionic and butyric acids to acetic acid, causing the total acid decreasing to 1500 mg/L. In contrast, Fe2+ caused an accumulation of all volatile fatty acids up to 4000 mg/L and aggravated acid inhibition, resulting in a significant reduction in MPR to 148 mL/gVS/d. In all treatments, the influence of ammonia nitrogen was not significant. This study provided a direction for the determination of engineering monitoring indicators and regulation measures in AD of VW.

Prevention of diabetic cardiomyopathy through metabolic amendments of myocardium by melatonin: a role beyond antioxidative efficiency

The alarming rise in diabetes throughout the world brings the scientist at the brink of finding a suitable compound that can impede glucotoxicity and insulin resistance involved development as well as progression of diabetes. Either devoid of insulin or resistance of cells to insulin brings forward the pancreatic tissue as the most vulnerably affected system. However, cardiac tissue, being the most exposed to circulation with high glucose content, is another target of hyperglycaemia. The remodelling of cardiac tissue in insulin resistant diabetic individuals includes cardiac hypertrophy along with misaligned diastolic and systolic functions. All these amendments cause declined cardiac contractility, the major indication of heart failure. The search for rationale behind such undesirable alterations put forward the involvement of altered cardiac metabolism in diabetes. Both carbohydrate and fatty acid metabolism have been found to be affected in diabetic individuals with declined glycolysis alongwith escalated lipolysis leading toward rise in fatty acid oxidation. Melatonin, with its antioxidative virtue prevents glucotoxicity induced excess reactive oxygen species (ROS) generation to afford protection to cellular systems. Nevertheless, the indole hinders ROS production by lowering both glucose and fatty acid accumulation through augmenting glycolysis along with diminishing lipolysis. Melatonin also expands its worth by keeping in order gluconeogenesis and glycogenesis pathways of metabolism in diabetic myocardium. The regulation of important metabolic pathways by melatonin in hyperglycaemic cardiac tissue assists the myocardium to maintain energy balance, the primary need for contractile behaviour. Hence, this review focuses on metabolic modulatory actions of melatonin in diabetic myocardium, which may encourage its usage as a saviour for diabetic cardiomyopathy.

Beneficial Effects of the Direct AMP-Kinase Activator PXL770 in In Vitro and In Vivo Models of X-Linked Adrenoleukodystrophy.

X-linked adrenoleukodystrophy (ALD) is a severe orphan disease caused by mutations in the peroxisomal ABCD1 transporter gene, leading to toxic accumulation of Very Long-Chain Fatty Acids (VLCFA - in particular C26:0) resulting in inflammation, mitochondrial dysfunction and demyelination. AMP-activated protein kinase (AMPK) is downregulated in ALD, and its activation is implicated as a therapeutic target. PXL770 is the first direct allosteric AMPK activator with established clinical efficacy and tolerability. Methods: We investigated its effects in ALD patient-derived fibroblasts/lymphocytes and Abcd1 KO mouse glial cells. Readouts included VLCFA levels, mitochondrial function and mRNA levels of proinflammatory genes and compensatory transporters (ABCD2-3). After PXL770 treatment in Abcd1 KO mice, we assessed VLCFA levels in tissues, sciatic nerve axonal morphology by electronic microscopy and locomotor function by open-field/balance-beam tests. Results: In patients' cells and Abcd1 KO glial cells, PXL770 substantially decreased C26:0 levels (by ∼90%), improved mitochondrial respiration, reduced expression of multiple inflammatory genes and induced expression of ABCD2-3 In Abcd1 KO mice, PXL770 treatment normalized VLCFA in plasma and significantly reduced elevated levels in brain (-25%) and spinal cord (-32%) versus untreated (P < 0.001). Abnormal sciatic nerve axonal morphology was also improved along with amelioration of locomotor function. Conclusion: Direct AMPK activation exerts beneficial effects on several hallmarks of pathology in multiple ALD models in vitro and in vivo, supporting clinical development of PXL770 for this disease. Further studies would be needed to overcome limitations including small sample size for some parameters, lack of additional in vivo biomarkers and incomplete pharmacokinetic characterization. SIGNIFICANCE STATEMENT: Adrenoleukodystrophy is a rare and debilitating condition with no approved therapies, caused by accumulation of very long-chain fatty acids. AMPK is downregulated in the disease and has been implicated as a potential therapeutic target. PXL770 is a novel clinical stage direct AMPK activator. In these studies, we used PXL770 to achieve preclinical validation of direct AMPK activation for this disease - based on correction of key biochemical and functional readouts in vitro and in vivo, thus supporting clinical development.