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Background Low-volume hypertonic solutions, such as half-molar lactate (LAC), may be a potential treatment used for fluid resuscitation. This study aimed to evaluate the underlying cardiovascular effects and mechanisms of LAC infusion compared to sodium-matched hypertonic sodium chloride (SAL). Methods Eight healthy male participants were randomized in a controlled, single-blinded, crossover study. Each participant received a four-hour infusion of LAC and SAL in a randomized order. Assessor-blinded echocardiography and blood samples were performed. The primary endpoint was cardiac output (CO) measured by echocardiography. Results During LAC infusion, circulating lactate levels increased by 1.9 mmol/L (95% CI 1.8–2.0 mmol/L, P  < 0.001) compared with SAL. CO increased by 1.0 L/min (95% CI 0.5–1.4 L/min, P  < 0.001), driven primarily by a significant increase in stroke volume of 11 mL (95% CI 4–17 mL, P  = 0.002), with no significant change in heart rate. Additionally, left ventricular ejection fraction improved by 5 percentage points ( P  < 0.001) and global longitudinal strain by 1.5 percentage points ( P  < 0.001). Preload indicators were elevated during SAL infusion compared with LAC infusion. Concomitantly, afterload parameters, including systemic vascular resistance and effective arterial elastance, were significantly decreased with LAC infusion compared with SAL, while mean arterial pressure remained similar. Indicators of contractility improved during LAC infusion. Conclusions In healthy participants, LAC infusion enhanced cardiac function, evidenced by increases in CO, stroke volume, and left ventricular ejection fraction compared with SAL. Indicators of contractility improved, afterload decreased, and preload remained stable. Therefore, LAC infusion may be an advantageous resuscitation fluid, particularly in patients with cardiac dysfunction. Clinical trial registrations https://clinicaltrials.gov/ct2/show/NCT04710875 . Registered 1 December 2020.

Two enantiomers of lactic acid exist. While L-lactic acid is a common compound of human metabolism, D-lactic acid is produced by some strains of microorganism or by some less relevant metabolic pathways. While L-lactic acid is an endogenous compound, D-lactic acid is a harmful enantiomer. Exposure to D-lactic acid can happen by various ways including contaminated food and beverages and by microbiota during some pathological states like short bowel syndrome. The exposure to D-lactic acid cannot be diagnosed because the common analytical methods are not suitable for distinguishing between the two enantiomers. In this review, pathways for D-lactic acid, pathological processes, and diagnostical and analytical methods are introduced followed by figures and tables. The current literature is summarized and discussed.

Lactic acid (LA) is an important platform chemical due to its significant applications in various fields and its use as a monomer for the production of biodegradable poly(lactic acid) (PLA). Free LA production is required to get rid of CaSO4, a waste material produced during fermentation at neutral pH which will lead to easy purification of LA required for the production of biodegradable PLA. Additionally, there is no need to use corrosive acids to release free LA from the calcium lactate produced during neutral fermentation. To date, several attempts have been made to improve the acid tolerance of lactic acid bacteria (LAB) by using both genome-shuffling approaches and rational design based on known mechanisms of LA tolerance and gene deletion in yeast strains. However, the lack of knowledge and the complexity of acid-tolerance mechanisms have made it challenging to generate LA-tolerant strains by simply modifying few target genes. Currently, adaptive evolution has proven an efficient strategy to improve the LA tolerance of individual/engineered strains. The main objectives of this article are to summarize the conventional biotechnological LA fermentation processes to date, assess their overall economic and environmental cost, and to introduce modern LA fermentation strategies for free LA production. In this review, we provide a broad overview of free LA fermentation processes using robust LAB that can ferment in acidic environments, the obstacles to these processes and their possible solutions, and the impact on future development of free LA fermentation processes commercially.

l -lactate modifies proteins through lactylation 1 , but how this process occurs is unclear. Here we identify the alanyl-tRNA synthetases AARS1 and AARS2 (AARS1/2) as intracellular l -lactate sensors required for l -lactate to stimulate the lysine lactylome in cells. AARS1/2 and the evolutionarily conserved Escherichia coli orthologue AlaRS bind to l -lactate with micromolar affinity and they directly catalyse l -lactate for ATP-dependent lactylation on the lysine acceptor end. In response to l -lactate, AARS2 associates with cyclic GMP–AMP synthase (cGAS) and mediates its lactylation and inactivation in cells and in mice. By establishing a genetic code expansion orthogonal system for lactyl-lysine incorporation, we demonstrate that the presence of a lactyl moiety at a specific cGAS amino-terminal site abolishes cGAS liquid-like phase separation and DNA sensing in vitro and in vivo. A lactyl mimetic knock-in inhibits cGAS, whereas a lactyl-resistant knock-in protects mice against innate immune evasion induced through high levels of l -lactate. MCT1 blockade inhibits cGAS lactylation in stressed mice and restores innate immune surveillance, which in turn antagonizes viral replication. Thus, AARS1/2 are conserved intracellular l -lactate sensors and have an essential role as lactyltransferases. Moreover, a chemical reaction process of lactylation targets and inactivates cGAS. The tRNA synthases AARS1 and AARS2 are identified as evolutionarily conserved sensors of intracellular l -lactate to mediate the global lysine lactylome.

Combat sports, encompassing a range of activities from striking and grappling to mixed and weapon-based disciplines, have witnessed a surge in popularity worldwide. These sports are demanding, requiring athletes to harness energy from different metabolic pathways to perform short, high-intensity activities interspersed with periods of lower intensity. While it is established that the anaerobic alactic (ATP-PC) and anaerobic lactic systems are pivotal for high-intensity training sessions typical in combat sports, the precise contribution of these systems, particularly in varied training modalities such as single (SMT) and intermittent (IST) forms of the 30-second Wingate test, remains inadequately explored. This study aims at comparing performance outputs, physiological responses and gender differences during the SMT and IST forms of the 30-second Wingate test. Thirty-three highly trained combat sports athletes (17 women, 16 men; 10 boxing, 8 wrestling, 8 taekwondo and 7 karate) randomly performed SMT and IST. The IST consisted of three 10-second all-out attempts separated by 30 seconds of passive recovery, whereas the SMT was a single 30-second maximal effort. Resting, exercise and post-exercise oxygen uptake and peak blood lactate value were used to determine the metabolic energy demands via the PCr-LA-O 2 method. The findings showed that total metabolic energy expenditure (TEE), ATP-PCr system contribution and the output of mechanical variables were higher in the IST than in the SMT form (all p<0.001). In contrast, the contribution of glycolytic and oxidative systems was higher in the SMT form (all p<0.001). However, exercise form and gender interaction were not significant (p>0.05). In combat sports, performance is not only determined by physiological and technical skills but also by metabolic energy input and efficiency. Therefore, our results can provide a comparison regarding the effects of exercise type and gender on metabolic energy metabolism to design the training of combat sports athletes.

Metabolic flux analysis in mice reveals that lactate often acts as the primary carbon source for the tricarboxylic acid cycle both in normal tissues and in tumour microenvironments. Lactate fuels the citric acid cycle Glucose is thought to be the primary source of fuel for the tricarboxylic acid (TCA) cycle, also known as the citric acid cycle, which produces important metabolites and energy. Sheng Hui et al . now perform whole-body metabolite analysis in mice. They find that circulating lactate rather than glucose can be a major source of carbon and hence fuel for TCA metabolism in both fed and fasting mice. They furthermore show this to be the case in tumour tissue. Mammalian tissues are fuelled by circulating nutrients, including glucose, amino acids, and various intermediary metabolites. Under aerobic conditions, glucose is generally assumed to be burned fully by tissues via the tricarboxylic acid cycle (TCA cycle) to carbon dioxide. Alternatively, glucose can be catabolized anaerobically via glycolysis to lactate, which is itself also a potential nutrient for tissues 1 and tumours 2 , 3 , 4 , 5 . The quantitative relevance of circulating lactate or other metabolic intermediates as fuels remains unclear. Here we systematically examine the fluxes of circulating metabolites in mice, and find that lactate can be a primary source of carbon for the TCA cycle and thus of energy. Intravenous infusions of 13 C-labelled nutrients reveal that, on a molar basis, the circulatory turnover flux of lactate is the highest of all metabolites and exceeds that of glucose by 1.1-fold in fed mice and 2.5-fold in fasting mice; lactate is made primarily from glucose but also from other sources. In both fed and fasted mice, 13 C-lactate extensively labels TCA cycle intermediates in all tissues. Quantitative analysis reveals that during the fasted state, the contribution of glucose to tissue TCA metabolism is primarily indirect (via circulating lactate) in all tissues except the brain. In genetically engineered lung and pancreatic cancer tumours in fasted mice, the contribution of circulating lactate to TCA cycle intermediates exceeds that of glucose, with glutamine making a larger contribution than lactate in pancreatic cancer. Thus, glycolysis and the TCA cycle are uncoupled at the level of lactate, which is a primary circulating TCA substrate in most tissues and tumours.

Hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopic imaging (MRSI) is a noninvasive metabolic-imaging modality that probes carbon flux in tissues and infers the state of metabolic reprograming in tumors. Prevailing models attribute elevated hyperpolarized [1-13C]pyruvate-to-[1-13C]lactate conversion rates in aggressive tumors to enhanced glycolytic flux and lactate dehydrogenase A (LDHA) activity (Warburg effect). By contrast, we find by cross-sectional analysis using genetic and pharmacological tools in mechanistic studies applied to well-defined genetically engineered cell lines and tumors that initial hyperpolarized [1-13C]pyruvate-to-[1-13C]lactate conversion rates as well as global conversion were highly dependent on and critically rate-limited by the transmembrane influx of [1-13C]pyruvate mediated predominately by monocarboxylate transporter-1 (MCT1). Specifically, in a cell-encapsulated alginate bead model, induced short hairpin (shRNA) knockdown or overexpression of MCT1 quantitatively inhibited or enhanced, respectively, unidirectional pyruvate influxes and [1-13C]pyruvate-to-[1-13C]lactate conversion rates, independent of glycolysis or LDHA activity. Similarly, in tumor models in vivo, hyperpolarized [1-13C]pyruvate-to-[1-13C]lactate conversion was highly dependent on and critically rate-limited by the induced transmembrane influx of [1-13C]pyruvate mediated by MCT1. Thus, hyperpolarized [1-13C]pyruvate MRSI measures primarily MCT1-mediated [1-13C]pyruvate transmembrane influx in vivo, not glycolytic flux or LDHA activity, driving a reinterpretation of this maturing new technology during clinical translation. Indeed, Kaplan–Meier survival analysis for patients with pancreatic, renal, lung, and cervical cancers showed that high-level expression of MCT1 correlated with poor overall survival, and only in selected tumors, coincident with LDHA expression. Thus, hyperpolarized [1-13C]pyruvate MRSI provides a noninvasive functional assessment primarily of MCT1 as a clinical biomarker in relevant patient populations.

Fermentation of various food stuffs by lactic acid bacteria is one of the oldest forms of food biopreservation. Bacterial antagonism has been recognized for over a century, but in recent years, this phenomenon has received more scientific attention, particularly in the use of various strains of lactic acid bacteria (LAB). Certain strains of LAB demonstrated antimicrobial activity against foodborne pathogens, including bacteria, yeast and filamentous fungi. Furthermore, in recent years, many authors proved that lactic acid bacteria have the ability to neutralize mycotoxin produced by the last group. Antimicrobial activity of lactic acid bacteria is mainly based on the production of metabolites such as lactic acid, organic acids, hydroperoxide and bacteriocins. In addition, some research suggests other mechanisms of antimicrobial activity of LAB against pathogens as well as their toxic metabolites. These properties are very important because of the future possibility to exchange chemical and physical methods of preservation with a biological method based on the lactic acid bacteria and their metabolites. Biopreservation is defined as the extension of shelf life and the increase in food safety by use of controlled microorganisms or their metabolites. This biological method may determine the alternative for the usage of chemical preservatives. In this study, the possibilities of the use of lactic acid bacteria against foodborne pathogens is provided. Our aim is to yield knowledge about lactic acid fermentation and the activity of lactic acid bacteria against pathogenic microorganisms. In addition, we would like to introduce actual information about health aspects associated with the consumption of fermented products, including probiotics.

Antimicrobial photodynamic therapy (aPDT) is increasingly being explored for treatment of periodontitis. Here, we investigated the effect of aPDT on human dental plaque bacteria in suspensions and biofilms in vitro using methylene blue (MB)-loaded poly(lactic-co-glycolic) (PLGA) nanoparticles (MB-NP) and red light at 660 nm. The effect of MB-NP-based aPDT was also evaluated in a clinical pilot study with 10 adult human subjects with chronic periodontitis. Dental plaque samples from human subjects were exposed to aPDT—in planktonic and biofilm phases—with MB or MB-NP (25 µg/mL) at 20 J/cm2 in vitro. Patients were treated either with ultrasonic scaling and scaling and root planing (US + SRP) or ultrasonic scaling + SRP + aPDT with MB-NP (25 µg/mL and 20 J/cm2) in a split-mouth design. In biofilms, MB-NP eliminated approximately 25% more bacteria than free MB. The clinical study demonstrated the safety of aPDT. Both groups showed similar improvements of clinical parameters one month following treatments. However, at three months ultrasonic SRP + aPDT showed a greater effect (28.82%) on gingival bleeding index (GBI) compared to ultrasonic SRP. The utilization of PLGA nanoparticles encapsulated with MB may be a promising adjunct in antimicrobial periodontal treatment.

Lactic acid can synthesize high value-added chemicals such as poly lactic acid. In order to further minimize the cost of lactic acid production, some effective strategies (e.g., effective mutagenesis and metabolic engineering) have been applied to increase productive capacity of lactic acid bacteria. In addition, low-cost cheap raw materials (e.g., cheap carbon source and cheap nitrogen source) are also used to reduce the cost of lactic acid production. In this review, we summarized the recent developments in lactic acid production, including efficient strain modification technology (high-efficiency mutagenesis means, adaptive laboratory evolution, and metabolic engineering), the use of low-cost cheap raw materials, and also discussed the future prospects of this field, which could promote the development of lactic acid industry.