The persistent hurdles of charge rapid recombination, inefficient use of light and utilization of sacrificial reagents have plagued the field of photocatalytic hydrogen evolution (PHE). In this research, tiny MoO2 nanoparticles of 10 nm in diameter were prepared through a straightforward solvothermal approach with a specific ratio of oleylamine and oleic acid as stabilizers. The critical factor in the synthesis process was found to be the ratio of oleylamine to oleic acid. Moreover, a two-phase interface assembly method facilitated the uniform deposition of MoO2 onto CdS nanorods. Due to the localized plasmonic-thermoelectric effect on the surface of MoO2 along with its abundant oxygen vacancies, the composite catalyst exhibited outstanding photo-utilization efficiency and an abundance of active sites. The CdS-MoO2 composite displayed a unique photochemical property in transforming lactic acid into pyruvic acid and generating hydrogen simultaneously. After exposure to artificial sunlight for 4 h, significant values of 4.7 and 3.7 mmol⋅g-1⋅h-1 were achieved for hydrogen production and pyruvic acid formation, respectively, exceeding CdS alone by 3.29 and 4.02-fold, while the selectivity of pyruvic acid was 95.68 %. Furthermore, the S-Scheme electron transport mechanism in the composites was elucidated using Electron Paramagnetic Resonance (EPR) spectroscopy, radical trapping experiments, energy band structure analysis, and the identification of critical intermediates in the process of selective oxidation. This work sheds light on the design and preparation of high-performance photocatalysts for biorefining coupled with efficient hydrogen evolution.

UNASSIGNED: Metabolism is inextricably linked to every aspect of cellular function. In addition to energy production and biosynthesis, metabolism plays a crucial role in regulating signal transduction and gene expression. Altered metabolic states have been shown to maintain aberrant signaling and transcription, contributing to diseases like cancer, cardiovascular disease, and neurodegeneration. Metabolic gene polymorphisms and defects are also associated with chronic pain conditions, as are increased levels of nerve growth factor (NGF). However, the mechanisms by which NGF may modulate sensory neuron metabolism remain unclear. This study demonstrated that intraplantar NGF injection reprograms sensory neuron metabolism. Nerve growth factor suppressed mitochondrial pyruvate oxidation and enhanced lactate extrusion, requiring 24 hours to increase lactate dehydrogenase A and pyruvate dehydrogenase kinase 1 (PDHK1) expression. Inhibiting these metabolic enzymes reversed NGF-mediated effects. Remarkably, directly disrupting mitochondrial pyruvate oxidation induced severe, persistent allodynia, implicating this metabolic dysfunction in chronic pain. Nanopore long-read sequencing of poly(A) mRNA uncovered extensive transcriptomic changes upon metabolic disruption, including altered gene expression, splicing, and poly(A) tail lengths. By linking metabolic disturbance of dorsal root ganglia to transcriptome reprogramming, this study enhances our understanding of the mechanisms underlying persistent nociceptive sensitization. These findings imply that impaired mitochondrial pyruvate oxidation may drive chronic pain, possibly by impacting transcriptomic regulation. Exploring these metabolite-driven mechanisms further might reveal novel therapeutic targets for intractable pain.

The laboratory-scale (in-vitro) microbial fermentation based on screening of process parameters (factors) and statistical validation of parameters (responses) using regression analysis. The recent trends have shifted from full factorial design towards more complex response surface methodology designs such as Box-Behnken design, Central Composite design. Apart from the optimisation methodologies, the listed designs are not flexible enough in deducing properties of parameters in terms of class variables. Machine learning algorithms have unique visualisations for the dataset presented with appropriate learning algorithms. The classification algorithms cannot be applied on all datasets and selection of classifier is essential in this regard. To resolve this issue, factor-response relationship needs to be evaluated as dataset and subsequent preprocessing could lead to appropriate results. The aim of the current study was to investigate the data-mining accuracy on the dataset developed using in-vitro pyruvate production using organic sources for the first time. The attributes were subjected to comparative classification on various classifiers and based on accuracy, multilayer perceptron (neural network algorithm) was selected as classifier. As per the results, the model showed significant results for prediction of classes and a good fit. The learning curve developed also showed the datasets converging and were linearly separable.

Complications of diabetes are often attributed to glucose and reactive dicarbonyl metabolites derived from glycolysis or gluconeogenesis, such as methylglyoxal. However, in the CNS, neurons and endothelial cells use lactate as energy source in addition to glucose, which does not lead to the formation of methylglyoxal and has previously been considered a safer route of energy consumption than glycolysis. Nevertheless, neurons and endothelial cells are hotspots for the cellular pathology underlying neurological complications in diabetes, suggesting a cause that is distinct from other diabetes complications and independent of methylglyoxal. Here, we show that in clinical and experimental diabetes plasma concentrations of dimethylglyoxal are increased. In a mouse model of diabetes, ilvb acetolactate-synthase-like (ILVBL, HACL2) is the enzyme involved in formation of increased amounts of dimethylglyoxal from lactate-derived pyruvate. Dimethylglyoxal reacts with lysine residues, forms Nε-3-hydroxy-2-butanonelysine (HBL) as an adduct, induces oxidative stress more strongly than other dicarbonyls, causes blood-brain barrier disruption, and can mimic mild cognitive impairment in experimental diabetes. These data suggest dimethylglyoxal formation as a pathway leading to neurological complications in diabetes that is distinct from other complications. Importantly, dimethylglyoxal formation can be reduced using genetic, pharmacological and dietary interventions, offering new strategies for preventing CNS dysfunction in diabetes.

Metformin is a common diabetes drug that may reduce lactate clearance by inhibiting mitochondrial oxidative phosphorylation, leading to metformin-associated lactic acidosis (MALA). As diabetes mellitus is a common chronic metabolic condition found in critically ill patients, pre-existing metformin use can often be found in critically ill patients admitted to the intensive care unit or the high dependency unit. The aim of this narrative mini review is therefore to update clinicians about MALA, and to provide a practical approach to its diagnosis and treatment. MALA in critically ill patients may be suspected in a patient who has received metformin and who has a high anion gap metabolic acidosis, and confirmed when lactate exceeds 5 mmol/L. Risk factors include those that reduce renal elimination of metformin (renal impairment from any cause, histamine-2 receptor antagonists, ribociclib) and excessive alcohol consumption (as ethanol oxidation consumes nicotinamide adenine dinucleotides that are also required for lactate metabolism). Treatment of MALA involves immediate cessation of metformin, supportive management, treating other concurrent causes of lactic acidosis like sepsis, and treating any coexisting diabetic ketoacidosis. Severe MALA requires extracorporeal removal of metformin with either intermittent hemodialysis or continuous kidney replacement therapy. The optimal time to restart metformin has not been well-studied. It is nonetheless reasonable to first ensure that lactic acidosis has resolved, and then recheck the kidney function post-recovery from critical illness, ensuring that the estimated glomerular filtration rate is 30 mL/min/1.73 m2 or better before restarting metformin.

Mitochondrial dysfunction in autism leads to impair the mitochondria\'s ability to synthesis adenosine triphosphate (ATP) by impairment citric acid cycle as well as increase anaerobic glycolysis. Aim - measuring and evaluating the levels of mitochondrial markers; including glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), malate dehydrogenase, and pyruvate kinase) in the autistic group and knowing the possibility of using these markers to diagnose children with autism spectrum disorder. A case-control study was done in the Al-Zahraa Teaching Hospital (Kut City, Iraq) on 100 Iraqi children (male and female), between (April 2023 and January 2024). Their ages ranged between 3 and 9 years. Among them were 50 patients enrolled as autistic group and 50 healthy enrolled as control group. Blood samples were collected and bioassays for GOT, GPT, pyruvate kinase, and malate dehydrogenase were measured by ELISA technique. The autistic group showed that the urine GOT, urine GPT, serum malate, and serum pyruvate levels in the ASD group was significantly higher (P<0.001) than the control group. The ROC analysis showed that urine GOT, urine GOT, serum malate and serum pyruvate had an accuracy level of (81%,71%,77%, and 80 %) and the area under the curve (AUC) was > 0.7 (0.8),0.7, 0.7(0.76), and 0.7(0.8) thus urine GOT, urine GPT, serum, malate, and serum pyruvate are a valid diagnostic marker. There was a significant difference in the mean urine and serum concentrations of mitochondrial markers (GOT, GPT, malate dehydrogenase, and pyruvate kinase) between autistic children and the control group due to mitochondrial dysfunction.

Non-alcoholic steatohepatitis (NASH) is characterized from its early stages by a profound remodeling of the liver microenvironment, encompassing changes in the composition and activities of multiple cell types and associated gene expression patterns. Hyperpolarized (HP) 13C MRI provides a unique view of the metabolic microenvironment, with potential relevance for early diagnosis of liver disease. Previous studies have detected changes in HP 13C pyruvate to lactate conversion, catalyzed by lactate dehydrogenase (LDH), with experimental liver injury. HP ∝ -ketobutyrate ( ∝ KB) is a close molecular analog of pyruvate with modified specificity for LDH isoforms, specifically attenuated activity with their LDHA-expressed subunits that dominate liver parenchyma. Building on recent results with pyruvate, we investigated HP ∝ KB in methionine-choline deficient (MCD) diet as a model of early-stage NASH. Similarity of results between this new agent and pyruvate (~ 50% drop in cytoplasmic reducing capacity), interpreted together with gene expression data from the model, suggests that changes are mediated through broad effects on intermediary metabolism. Plausible mechanisms are depletion of the lactate pool by upregulation of gluconeogenesis (GNG) and pentose phosphate pathway (PPP) flux, and a possible shift toward increased lactate oxidation. These changes may reflect high levels of oxidative stress and/or shifting macrophage populations in NASH.

The phosphoenol pyruvate-oxaloacetate-pyruvate-derived amino acids (POP-AAs) comprise native intermediates in cellular metabolism, within which the phosphoenol pyruvate-oxaloacetate-pyruvate (POP) node is the switch point among the major metabolic pathways existing in most living organisms. POP-AAs have widespread applications in the nutrition, food, and pharmaceutical industries. These amino acids have been predominantly produced in Escherichia coli and Corynebacterium glutamicum through microbial fermentation. With the rapid increase in market requirements, along with the global food shortage situation, the industrial production capacity of these two bacteria has encountered two bottlenecks: low product conversion efficiency and high cost of raw materials. Aiming to push forward the update and upgrade of engineered strains with higher yield and productivity, this paper presents a comprehensive summarization of the fundamental strategy of metabolic engineering techniques around phosphoenol pyruvate-oxaloacetate-pyruvate node for POP-AA production, including L-tryptophan, L-tyrosine, L-phenylalanine, L-valine, L-lysine, L-threonine, and L-isoleucine. Novel heterologous routes and regulation methods regarding the carbon flux redistribution in the POP node and the formation of amino acids should be taken into consideration to improve POP-AA production to approach maximum theoretical values. Furthermore, an outlook for future strategies of low-cost feedstock and energy utilization for developing amino acid overproducers is proposed.

Pyruvate dehydrogenase (PDH) catalyses the irreversible decarboxylation of pyruvate to acetyl-CoA, which feeds the tricarboxylic acid cycle. We investigated how the loss of PDH affects metabolism in Pseudomonas putida. PDH inactivation resulted in a strain unable to utilize compounds whose assimilation converges at pyruvate, including sugars and several amino acids, whereas compounds that generate acetyl-CoA supported growth. PDH inactivation also resulted in the loss of carbon catabolite repression (CCR), which inhibits the assimilation of non-preferred compounds in the presence of other preferred compounds. Pseudomonas putida can degrade many aromatic compounds, most of which produce acetyl-CoA, making it useful for biotransformation and bioremediation. However, the genes involved in these metabolic pathways are often inhibited by CCR when glucose or amino acids are also present. Our results demonstrate that the PDH-null strain can efficiently degrade aromatic compounds even in the presence of other preferred substrates, which the wild-type strain does inefficiently, or not at all. As the loss of PDH limits the assimilation of many sugars and amino acids and relieves the CCR, the PDH-null strain could be useful in biotransformation or bioremediation processes that require growth with mixtures of preferred substrates and aromatic compounds.

Transdermal behavior is a critical aspect of studying delivery systems and evaluating the efficacy of cosmetics. However, existing methods face challenges such as lengthy experiments, high cost, and limited model accuracy. Therefore, developing accurate transdermal models is essential for formulation development and effectiveness assessment. In this study, we developed a multiscale model to describe the transdermal behavior of active ingredients in the stratum corneum. Molecular dynamics simulations were used to construct lipid bilayers and determine the diffusion coefficients of active ingredients in different regions of these bilayers. These diffusion coefficients were integrated into a multilayer lipid pathway model using finite element simulations. The simulation results were in close agreement with our experimental results for three active ingredients (mandelic acid (MAN), nicotinamide (NIC), and pyruvic acid (PYR)), demonstrating the effectiveness of our multiscale model. This research provides valuable insights for advancing transdermal delivery methods.