Relationship between Lactate Dehydrogenase and survival in patients with non-small cell lung cancer receiving immunotherapy. / Relación entre el lactato deshidrogenasa y la supervivencia en pacientes con cáncer de pulmón no microcítico que reciben tratamiento con inmunoterapia.

OBJECTIVE: The expression level of programmed death ligand 1 (PD-L1) is the only approved biomarker for predicting response to immunotherapy, yet its efficacy is not always consistent. Lactate dehydrogenase (LDH) has been associated with tumor aggressiveness and poorer prognosis across various cancer types and may serve as a useful biomarker for monitoring treatment response. The objective of this study is to analyze the relationship between LDH levels prior to the start of treatment with immune checkpoint inhibitors (ICIs) and clinical outcomes in patients with non-small cell lung cancer (NSCLC). METHOD: A retrospective study was conducted including patients diagnosed with NSCLC who were treated with at least three cycles of immunotherapy. Data on demographics, clinical and pathological characteristics, treatment received, pre-treatment LDH levels, and clinical outcomes such as treatment response and overall survival (OS) were analyzed. RESULTS: A total of 181 patients diagnosed with NSCLC were included. Elevated pre-treatment LDH levels (more than 244 U/l) were associated with significantly reduced OS. The median survival was 548 days in patients with LDH less than 244 U/l, compared to 332 days in those with LDH more than 244 U/l (p = 0.037). Among men, OS was greater in the LDH less than 244 U/l group (623 days) versus 332 days in the LDH more than 244 U/l group (p = 0.043). In patients with metastatic disease, OS was higher in those with LDH less than 244 U/l (474 days) compared to 249 days in those with LDH more than 244 U/l (p = 0.023). In patients receiving both immunotherapy and chemotherapy, OS was greater in those with LDH less than 244 U/l (623 days) compared to 281 days in the LDH more than 244 U/l group (p = 0.042). CONCLUSIONS: High levels of LDH prior to the start of treatment with ICIs are associated with lower treatment efficacy and a worse prognosis of the disease, especially in male, metastatic patients with a PD-L1 expression level less than 1%.

Recombinant lactate-assimilating cyanobacteria reduce high-concentration culture-associated cytotoxicity in mammalian cells.

In the fields of cultured meat, biopharmaceuticals, cell therapy, and tissue engineering, large numbers of mammalian cells are required; thus, highly-concentrated cell cultures are widely adopted. In general, such cultures can lead to cell damage caused by waste product accumulation and nutritional inadequacy. In this study, a novel co-culture system where the recombinant lactate-assimilating cyanobacterial strain, KC0110, derived from euryhaline Picosynechococcus sp. PCC 7002, and mammalian muscle cells cultured across porous membranes been developed. By using the KC0110 strain, the amount of ammonium and lactate excreted from C2C12 mouse muscle cells into the culture significantly decreased. Importantly, pyruvate and some amino acids, including pyruvate-derived amino acids, also increased significantly compared to those in monoculture of C2C12 cells. It is believed that the organic acids secreted by the KC0110 strain enhance the growth of mammalian cells, leading to a reduction in high-concentration culture-induced mammalian cell damage [lactate dehydrogenase (LDH) release] through cyanobacterial co-culture. These results show that, through co-cultivation with cyanobacteria, it is possible to culture mammalian cells, alleviating cell damage, even in highly-concentrated cultures. This study demonstrated an in vitro "symbiotic circular system" that can interchange metabolites produced by phototrophs and mammalian cells.

Early intervention of 5% albumin shown superior control of vascular integrity and function compared to ringer's lactatein hospitalized adult with grade I & II Dengue hemorrhagic fever: a multicenter randomized controlled trial in Indonesia.

BACKGROUND: Dengue virus remains a major public health problem with one of the hallmark pathologies is the vascular leakage caused by endothelial dysfunction which can lead to Dengue Hemorrhagic Fever (DHF) manifestation. In the status quo, no specific therapy has been discovered but rather heavily relies on judicious and frequent monitoring of intravenous fluids administration. The current guideline has discussed the roles of fluid therapy during the Dengue Shock Syndrome (DSS) stage, however, administration of early fluid intervention for DHF grade I and II remains uncharted territory. In addition, the choice and timing of colloid administration remains underexplored. As one of the widely available colloids, 5% albumin has known physiological properties that potentially minimize plasma leakage. Therefore, this study aimed to evaluate the benefit of early intervention of 5% albumin in adults with DHF in the hope of preventing the lethal progression to DSS and further, shorten the length of stay (LOS) for patients. METHODS: We conducted a multicenter, open-labeled, randomized controlled trial in Jakarta and Banten to compare the effect of early intervention with 5% albumin in adult patients with DHF compared to Ringer's Lactate (RL). Statistical analyses were conducted using unpaired t-test and Mann-Whitney for normally and abnormally distributed data respectively. RESULTS: Adult patients with a diagnosis of DHF grade I and II that being hospitalized to receive the early intervention of 5% albumin had significantly lower levels of hemoconcentration 4, 12, and 24 h (p = 0.002, 0.001, 0.003, respectively), higher platelet counts 4 h (p = 0.036), higher serum albumin levels 48 h (p = 0.036), lower proteinuria 24 and 48 h post-albumin administration (p < 0.001, < 0.001, respectively), and shorter LOS (p < 0.001) when compared to the RL group. CONCLUSION: Early intervention of 5% albumin showed better control on vascular integrity and function compared to ringer lactate in hospitalized adults with grade I & II DHF, thus halting the progression of DHF into DSS and other related complications which leads to faster recovery and shorter length of stay. TRIAL REGISTRATION: The study was registered to www. CLINICALTRIAL: gov with trial registration number NCT04076254, and registration date October 31st 2016.

Advanced biomarker clustering analysis reveals mortality predictors in burn patients with sepsis.

This study addresses the challenge of predicting mortality in sepsis among burn patients. Given the heterogeneity of sepsis, especially in the context of burn injuries, this study aims to identify reliable biomarkers for mortality prediction. The study is a retrospective review, focusing on the evaluation of various biomarkers and their changes over time in a burn patient cohort. Conducted in the Burn Intensive Care Unit of Hangang Sacred Heart Hospital, the study involved a retrospective review of 1,659 adult burn patients from January 2010 to December 2022. Key biomarkers analyzed include lactate levels, pH, platelets, procalcitonin, and others. Advanced clustering methodologies, such as dynamic time warping and hierarchical clustering, were utilized to classify patients into distinct groups based on their biomarker profiles and clinical outcomes. The study identified four patient clusters with unique lactate level trajectories. Significant findings include the identification of procalcitonin, pH, and platelets as key predictors of mortality, with varying degrees of efficacy across different clusters. For instance, in the "Persistent Rise" cluster, pH and platelet count showed Area Under the Curve (AUC) values of 0.756 and 0.753, respectively, indicating their strong predictive power. The study concludes that a combination of biomarkers, especially lactate dynamics, can effectively predict mortality in burn-induced sepsis. The results advocate for a more personalized approach in managing sepsis in burn patients, considering the specific biomarker trajectories. These findings are crucial for enhancing treatment strategies and improving patient outcomes in burn care.

Utilizing point-of-care lactate testing for rapid prediction of clinical outcomes in patients with acute gastrointestinal bleeding in the emergency department.

Objectives: We aimed to rapidly predict the prognosis of patients who present to the emergency department (ED) with acute gastrointestinal bleeding (AGIB) using point-of-care (POC) lactate testing. Methods: This single-center retrospective observational study included 327 patients (survival group, 287; non-survival group, 40) who presented to the ED with AGIB between March 2021 and February 2022. We compared POC-measured lactate levels with laboratory-measured lactate levels using Pearson's correlation. Multivariate logistic regression analysis was used to identify early predictors of in-hospital mortality and correlated clinical outcomes. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff for POC-measured lactate levels for predicting in-hospital mortality, and the ROC curves for POC-measured lactate levels and AIMS65 scores were compared using the DeLong test. Results: POC-measured lactate levels strongly correlated with laboratory-measured lactate levels (R2 = 0.82). Patients in the non-survival group had higher POC-measured lactate levels than did those in the survival group (2.6 mmol/L vs. 1.4 mmol/L, p < 0.001). POC-measured lactate level, age, systolic blood pressure, heart rate, and malignancy were identified as early predictors of in-hospital mortality (adjusted odds ratio [aOR] for POC-measured lactate levels: 1.15; 95 % confidence interval [CI] 1.02-1.30). The optimal POC-measured lactate level cutoff was 3.2 mmol/L. Areas under the ROC curves for POC-measured lactate level and the AIMS65 score were 0.70 and 0.73, respectively, showing statistical compatibility. Higher POC-measured lactate levels correlated with ICU admission, blood transfusion, and mechanical ventilation (aOR: 1.16, 95 % CI 1.05-1.27; 1.16, 1.04-1.30; and 1.31, 1.13-1.53, respectively]. Further, the hyperlactatemia subgroup (POC-measured lactate level ≥3.2 mmol/L) exhibited a lower survival probability in the Kaplan-Meier survival analysis (p < 0.01). Conclusions: Our study shows that rapidly obtainable POC-measured lactate levels are valuable for predicting critical outcomes in AGIB patients and should be considered an early prognostic indicator for in-hospital mortality in the ED.

Role of Lactate Dehydrogenase as a Biomarker of Early Cardiac Remodeling: A Cross-Sectional Study.

BACKGROUND: Lactate dehydrogenase (LDH) isoenzyme assay was used widely in the past to diagnose myocardial infarction (MI). Recent studies show that lactate dehydrogenase seems to be a promising biomarker of adverse left ventricular remodeling. OBJECTIVES: Higher levels of these biomarkers were associated with lower odds for favorable reverse remodeling in patients with MI. METHODS: The study was performed on patients with the first occurrence of acute myocardial infarction (ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI)), aged 34 to 80 years who underwent catheterization at the admission or during their hospital stay depending on indications. In this study, we compared peak levels of lactate dehydrogenase (LDH) and left ventricular ejection fraction (LVEF). Peak values of LDH were used from the second to the fourth day of hospitalization. Echocardiography has been done in the first 72 hours, which represents an early phase of cardiac remodeling. The ejection fraction was evaluated using the Simpson method. RESULTS: Spearman's rank test showed a negative, statistically significant correlation between LDH and ejection fraction ρ(80)=-0.543, p<0.001. Weighted least squares regression model included LDH concentration, age, and type of myocardial infarction (STEMI/NSTEMI), and the slope coefficient for the LDH level was -0.010 (95% confidence interval (CI): -0.013 to -0.006). With each unit of LDH increase, there was a decrease of 0.01% in left ventricular ejection fraction when age and type of myocardial infarction were held constant. CONCLUSION: The increased LDH level could be a new predictor for early myocardial remodeling after the first occurrence of myocardial infarction independent of age and type of myocardial infarction.

Tumor-Selective Nano-Dispatcher Enforced Cancer Immunotherapeutic Effects via Regulating Lactate Metabolism and Activating Toll-Like Receptors.

The development of tumors relies on lactate metabolic reprogramming to facilitate their unchecked growth and evade immune surveillance. This poses a significant challenge to the efficacy of antitumor immunity. To address this, a tumor-selective nano-dispatcher, PIMDQ/Syro-RNP, to enforce the immunotherapeutic effect through regulation of lactate metabolism and activation of toll-like receptors is developed. By using the tumor-targeting properties of c-RGD, the system can effectively deliver monocarboxylate transporters 4 (MCT4) inhibitor (Syro) to inhibit lactate efflux in tumor cells, leading to decreased lactate levels in the tumor microenvironment (TME) and increased accumulation within tumor cells. The reduction of lactate in TME will reduce the nutritional support for regulatory T cells (Tregs) and promote the effector function of T cells. The accumulation of lactate in tumor cells will lead to tumor death due to cellular acidosis. In addition, it will also reduce the uptake of glucose by tumor cells, reduce nutrient plunder, and further weaken the inhibition of T cell function. Furthermore, the pH-responsive release of Toll-like receptors (TLR) 7/8 agonist IMDQ within the TME activates dendritic cells (DCs) and promotes the infiltration of T cells. These findings offer a promising approach for enhancing tumor immune response through targeted metabolic interventions.

Lactate's impact on immune cells in sepsis: unraveling the complex interplay.

Lactate significantly impacts immune cell function in sepsis and septic shock, transcending its traditional view as just a metabolic byproduct. This review summarizes the role of lactate as a biomarker and its influence on immune cell dynamics, emphasizing its critical role in modulating immune responses during sepsis. Mechanistically, key lactate transporters like MCT1, MCT4, and the receptor GPR81 are crucial in mediating these effects. HIF-1α also plays a significant role in lactate-driven immune modulation. Additionally, lactate affects immune cell function through post-translational modifications such as lactylation, acetylation, and phosphorylation, which alter enzyme activities and protein functions. These interactions between lactate and immune cells are central to understanding sepsis-associated immune dysregulation, offering insights that can guide future research and improve therapeutic strategies to enhance patient outcomes.

Machine-learning-based evaluation of the usefulness of lactate for predicting neonatal mortality in preterm infants.

BACKGROUND: Unlike in adult and pediatric patients, the usefulness of lactate in preterm infants has not been thoroughly discussed. This study aimed to evaluate whether the lactate level in the first hours of life is an important factor associated with neonatal death in very-low-birth-weight (VLBW) preterm infants. METHODS: Electronic medical records from a level 4 neonatal intensive care unit in South Korea were reviewed to obtain perinatal and neonatal outcomes. Data on lactate levels of preterm infants in the first 12 h of life were collected. Neonatal mortality and morbidities were compared based on lactate levels. Subsequently, machine-learning models incorporating 20 independent variables, both with and without lactate, were compared for model performances and feature importance of lactate for predicting in-hospital mortality in the applicable models. RESULTS: One hundred and sixty-eight preterm infants were included. Death rates on days 7 and 30 of life (D30-mortality) were significantly higher in infants with high lactate levels (≥3rd interquartile range) than in those with lower levels (<3rd interquartile range). Though statistically insignificant, the overall in-hospital mortality was more than twice as high in the high lactate level group than in the lower lactate level group. Based on the machine learning results, Random Forest, Gradient Boosting, and LightGBM models all showed greater area under the curves when lactate was included. Lactate consistently ranked in the variables of top five feature importance, particularly showing the greatest value in the Gradient Boosting model. CONCLUSION: Lactate levels during the early hours of life may be an important factor associated with in-hospital death of preterm VLBW infants. Based on the enhanced performance of the above-mentioned machine learning models, lactate levels in the early postnatal period may add to assessing the clinical status and predicting the hospital course in this population.

Prognostic risk score and index including the platelet-to-lymphocyte ratio and lactate dehydrogenase in patients with metastatic or unresectable urothelial carcinoma treated with immune checkpoint inhibitors.

BACKGROUND: Avelumab and pembrolizumab are administered after platinum-based chemotherapy for the treatment of metastatic urothelial carcinoma. We explored the prognostic factors and risk scores for predicting the outcomes of metastatic or unresectable urothelial carcinoma at the start of treatment with immune checkpoint inhibitors. METHODS: This retrospective study included patients with metastatic or unresectable urothelial carcinoma treated with avelumab or pembrolizumab after platinum-based chemotherapy between January 2017 and December 2022. Prognostic factors, including patient and tumor characteristics and blood data at the initiation of immune checkpoint inhibitor therapy, were examined. RESULTS: This study included 36 and 207 patients treated with avelumab and pembrolizumab, respectively, for metastatic or unresectable urothelial carcinoma. Eastern Cooperative Oncology Group performance status, presence of visceral metastases, platelet-to-lymphocyte ratio and lactate dehydrogenase levels were independent prognostic factors for predicting overall survival. The median overall survival of patients in the risk-score model was 58.5 months (score zero), 27.9 months (one), 13.1 months (two) and 3.9 months (three or higher). The C-index for overall survival was 0.718 for the newly developed risk score compared with 0.679 for the Bellmunt score and 0.703 for the Bellmunt-C-reactive protein score. Additionally, the C-index for overall survival using the immune prognostic index derived from lactate dehydrogenase and the platelet-to-lymphocyte ratio was 0.646 compared with 0.615 for the Lung Immune Prognostic Index. CONCLUSIONS: A risk score that includes the platelet-to-lymphocyte ratio and lactate dehydrogenase may serve as a useful model for predicting prognosis following the initiation of immune checkpoint inhibitors in patients with metastatic or unresectable urothelial carcinoma.

Tissue derivatization for visualizing lactate and pyruvate in mouse testis tissues using matrix-assisted laser desorption/ionization-mass spectrometry imaging.

Pyruvate and lactate are the final metabolites of the glycolytic system that are formed under oxygen-rich and anaerobic conditions, respectively. They play an important role in energy metabolism. Obtaining a tissue distribution image of pyruvate and lactate holds great significance in molecular biology because the glycolytic system plays an essential role in diseases, such as tumors and diabetes; microbial activities, such as alcohol production and lactic acid fermentation; and maintaining homeostasis in the gut environment. However, it is difficult to obtain images of the distribution of in vivo metabolites because of the low detection sensitivities of current methods. In this study, a novel derivatization method for pyruvate and lactate was developed using matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to detect pyruvate and lactate in vivo and obtain biodistribution images. We investigated derivatization methods using readily available 3-nitrophenylhydrazine (3NPH), the addition of which improves the sensitivity of pyruvate detection, and the distribution of pyruvate in mouse testes was successfully visualized. Furthermore, the distribution of lactate in the mouse testes could be visualized, and improved detection sensitivity for the main metabolites of the tricarboxylic acid cycle was demonstrated. This derivatization method can be used to detect carboxyl-containing metabolites, including pyruvate, via MALDI-MSI. Furthermore, 3NPH forms amide bonds with carbonyl, phosphate, and carboxyl groups, suggesting the possibility of visualizing its distribution in many metabolites.

Differences in motivational dynamics between experienced cyclists and untrained participants during an incremental endurance exercise task.

PURPOSE: The conflict between the desire to reduce effort during exercise and the performance goal of the exercise task contributes to explaining endurance exercise performance. However, whether the trajectories of these two motivational responses systematically differ across individuals with different characteristics is poorly understood. The present study examined whether changes in desire to reduce effort and performance goal value across moderate, heavy, and severe exercise intensity domains differed between cyclists and untrained, but active participants. METHODS: Fifty participants (14 cyclists and 36 untrained) completed an incremental step test on a cycle ergometer, in which work rate was increased by 25 W every 4 min until voluntary exhaustion. Desire to reduce effort, performance goal value, and blood lactate concentration (for determination of exercise intensity domains) were measured every 4 min and the data were analysed using multilevel modelling. RESULTS: Desire to reduce effort increased quicker for untrained participants in the moderate exercise intensity domain (b = 1.66, p < .001) and across the whole trial (b = 1.64, p < .001), compared to cyclists (b = .69, and b = 1.14, respectively, both p < .001). Untrained participants reported similar performance goal value at the beginning of the trial (b = 16.02, p < .001), compared to cyclists (b = 17.25, p < .001). Beyond moderate intensities, the performance goal value decreased significantly for the untrained participants (b = -.70, p < .001) but significantly increased for cyclists (b = .45, p = .01). This pattern was also observed when focusing solely on the severe intensity domain (cyclists: b = .90, p < .001; untrained: b = -.84, p < .001). CONCLUSION: There are distinct differences in the desire to reduce effort and performance goal value between cyclists and untrained athletes. Identifying these systematic differences enhances the credibility of the desire-goal conflict framework in explaining endurance performance and provides insight into the type and timing of interventions that might be successful in improving performance.

Agreement Between Heart Rate Variability - Derived vs. Ventilatory and Lactate Thresholds: A Systematic Review with Meta-Analyses.

BACKGROUND: Determining thresholds by measuring blood lactate levels (lactate thresholds) or gas exchange (ventilatory thresholds) that delineate the different exercise intensity domains is crucial for training prescription. This systematic review with meta-analyses aims to assess the overall validity of the first and second heart rate variability - derived threshold (HRVT1 and HRVT2, respectively) by computing global effect sizes for agreement and correlation between HRVTs and reference - lactate and ventilatory (LT-VTs) - thresholds. Furthermore, this review aims to assess the impact of subjects' characteristics, HRV methods, and study protocols on the agreement and correlation between LT-VTs and HRVTs. METHODS: Systematic computerised searches for studies determining HRVTs during incremental exercise in humans were conducted. The agreements and correlations meta-analyses were conducted using a random-effect model. Causes of heterogeneity were explored by subgroup analysis and meta-regression with subjects' characteristics, incremental exercise protocols, and HRV methods variables. The methodological quality was assessed using QUADAS-2 and STARDHRV tools. The risk of bias was assessed by funnel plots, fail-safe N test, Egger's test of the intercept, and the Begg and Mazumdar rank correlation test. RESULTS: Fifty included studies (1160 subjects) assessed 314 agreements (95 for HRVT1, 219 for HRVT2) and 246 correlations (82 for HRVT1, 164 for HRVT2) between LT-VTs and HRVTs. The standardized mean differences were trivial between HRVT1 and LT1-VT1 (SMD = 0.08, 95% CI -0.04-0.19, n = 22) and between HRVT2 and LT2-VT2 (SMD = -0.06, 95% CI -0.15-0.03, n = 42). The correlations were very strong between HRVT1 and LT1-VT1 (r = 0.85, 95% CI 0.75-0.91, n = 22), and between HRVT2 and LT2-VT2 (r = 0.85, 95% CI 0.80-0.89, n = 41). Moreover, subjects' characteristics, type of ergometer, or initial and incremental workload had no impact on HRVTs determination. CONCLUSION: HRVTs showed trivial differences and very strong correlations with LT-VTs and might thus serve as surrogates. These results emphasize the usefulness of HRVTs as promising, accessible, and cost-effective means for exercise and clinical prescription purposes.

A patent review of lactate dehydrogenase inhibitors (2014-present).

INTRODUCTION: Lactate dehydrogenase (LDH) is a key enzyme in glycolysis responsible for the conversion of pyruvate into lactate and vice versa. Lactate plays a crucial role in tumor progression and metastasis; therefore, reducing lactate production by inhibiting LDH is considered an optimal strategy to tackle cancer. Additionally, dysregulation of LDH activity is correlated with other pathologies, such as cardiovascular and neurodegenerative diseases as well as primary hyperoxaluria, fibrosis and cryptosporidiosis. Hence, LDH inhibitors could serve as potential therapeutics for treating these pathological conditions. AREAS COVERED: This review covers patents published since 2014 up to the present in the Espacenet database, concerning LDH inhibitors and their potential therapeutic applications. EXPERT OPINION: Over the past 10 years, different compounds have been identified as LDH inhibitors. Some of them are derived from the chemical optimization of already known LDH inhibitors (e.g. pyrazolyl derivatives, quinoline 3-sulfonamides), while others belong to newly identified chemical classes of LDH inhibitors. LDH inhibition has proven to be a promising therapeutic strategy not only for preventing human pathologies, but also for treating animal diseases. The published patents from both academia and the pharmaceutical industry highlight the persistent high interest of the scientific community in developing efficient LDH inhibitors.

Acute psycho-physiological responses to submaximal constant-load cycling under intermittent hypoxia-hyperoxia vs. hypoxia-normoxia in young males.

Background: Hypoxia and hyperoxia can affect the acute psycho-physiological response to exercise. Recording various perceptual responses to exercise is of particular importance for investigating behavioral changes to physical activity, given that the perception of exercise-induced pain, discomfort or unpleasure, and a low level of exercise enjoyment are commonly associated with a low adherence to physical activity. Therefore, this study aimed to compare the acute perceptual and physiological responses to aerobic exercise under intermittent hypoxia-hyperoxia (IHHT), hypoxia-normoxia (IHT), and sustained normoxia (NOR) in young, recreational active, healthy males. Methods: Using a randomized, single-blinded, crossover design, 15 males (age: 24.5 ± 4.2 yrs) performed 40 min of submaximal constant-load cycling (at 60% peak oxygen uptake, 80 rpm) under IHHT (5 × 4 min hypoxia and hyperoxia), IHT (5 × 4 min hypoxia and normoxia), and NOR. Inspiratory fraction of oxygen during hypoxia and hyperoxia was set to 14% and 30%, respectively. Heart rate (HR), total hemoglobin (tHb) and muscle oxygen saturation (SmO2) of the right vastus lateralis muscle were continuously recorded during cycling. Participants' peripheral oxygen saturation (SpO2) and perceptual responses (i.e., perceived motor fatigue, effort perception, perceived physical strain, affective valence, arousal, motivation to exercise, and conflict to continue exercise) were surveyed prior, during (every 4 min), and after cycling. Prior to and after exercise, peripheral blood lactate concentration (BLC) was determined. Exercise enjoyment was ascertained after cycling. For statistical analysis, repeated measures analyses of variance were conducted. Results: No differences in the acute perceptual responses were found between conditions (p ≥ 0.059, ηp 2 ≤ 0.18), while the physiological responses differed. Accordingly, SpO2 was higher during the hyperoxic periods during the IHHT compared to the normoxic periods during the IHT (p < 0.001, ηp 2 = 0.91). Moreover, HR (p = 0.005, ηp 2 = 0.33) and BLC (p = 0.033, ηp 2 = 0.28) were higher during IHT compared to NOR. No differences between conditions were found for changes in tHb (p = 0.684, ηp 2 = 0.03) and SmO2 (p = 0.093, ηp 2 = 0.16). Conclusion: IHT was associated with a higher physiological response and metabolic stress, while IHHT did not lead to an increase in HR and BLC compared to NOR. In addition, compared to IHT, IHHT seems to improve reoxygenation indicated by a higher SpO2 during the hyperoxic periods. However, there were no differences in perceptual responses and ratings of exercise enjoyment between conditions. These results suggest that replacing normoxic by hyperoxic reoxygenation-periods during submaximal constant-load cycling under intermittent hypoxia reduced the exercise-related physiological stress but had no effect on perceptual responses and perceived exercise enjoyment in young recreational active healthy males.

Expanded genome and proteome reallocation in a novel, robust Bacillus coagulans strain capable of utilizing pentose and hexose sugars.

Bacillus coagulans, a Gram-positive thermophilic bacterium, is recognized for its probiotic properties and recent development as a microbial cell factory. Despite its importance for biotechnological applications, the current understanding of B. coagulans' robustness is limited, especially for undomesticated strains. To fill this knowledge gap, we characterized the metabolic capability and performed functional genomics and systems analysis of a novel, robust strain, B. coagulans B-768. Genome sequencing revealed that B-768 has the largest B. coagulans genome known to date (3.94 Mbp), about 0.63 Mbp larger than the average genome of sequenced B. coagulans strains, with expanded carbohydrate metabolism and mobilome. Functional genomics identified a well-equipped genetic portfolio for utilizing a wide range of C5 (xylose, arabinose), C6 (glucose, mannose, galactose), and C12 (cellobiose) sugars present in biomass hydrolysates, which was validated experimentally. For growth on individual xylose and glucose, the dominant sugars in biomass hydrolysates, B-768 exhibited distinct phenotypes and proteome profiles. Faster growth and glucose uptake rates resulted in lactate overflow metabolism, which makes B. coagulans a lactate overproducer; however, slower growth and xylose uptake diminished overflow metabolism due to the high energy demand for sugar assimilation. Carbohydrate Transport and Metabolism (COG-G), Translation (COG-J), and Energy Conversion and Production (COG-C) made up 60%-65% of the measured proteomes but were allocated differently when growing on xylose and glucose. The trade-off in proteome reallocation, with high investment in COG-C over COG-G, explains the xylose growth phenotype with significant upregulation of xylose metabolism, pyruvate metabolism, and tricarboxylic acid (TCA) cycle. Strain B-768 tolerates and effectively utilizes inhibitory biomass hydrolysates containing mixed sugars and exhibits hierarchical sugar utilization with glucose as the preferential substrate.IMPORTANCEThe robustness of B. coagulans makes it a valuable microorganism for biotechnology applications; yet, this phenotype is not well understood at the cellular level. Through phenotypic characterization and systems analysis, this study elucidates the functional genomics and robustness of a novel, undomesticated strain, B. coagulans B-768, capable of utilizing inhibitory switchgrass biomass hydrolysates. The genome of B-768, enriched with carbohydrate metabolism genes, demonstrates high regulatory capacity. The coordination of proteome reallocation in Carbohydrate Transport and Metabolism (COG-G), Translation (COG-J), and Energy Conversion and Production (COG-C) is critical for effective cell growth, sugar utilization, and lactate production via overflow metabolism. Overall, B-768 is a novel, robust, and promising B. coagulans strain that can be harnessed as a microbial biomanufacturing platform to produce chemicals and fuels from biomass hydrolysates.

Improving Glycerol Electrooxidation Performance on Nanocubic PtCo Catalysts.

As glycerol (GLY) has emerged as a highly functional and cheap platform molecule and as an abundant biodiesel production byproduct, possible conversion methods have been investigated. One of the promising approaches is the glycerol electrooxidation (GEOR) on noble metal-based catalysts. Although noble metals, especially Pt, are generally very stable at different pH and highly selective toward three-carbon (C3) products, their electrocatalytic performance can be further improved by morphology tuning and alloying with non-noble metals like Co. In the present study, cubic PtxCo100-x (x = 100, 80, and 60) nanoparticles were investigated in an alkaline medium at 20 and 40 °C. The effect of the composition and reaction conditions on the selectivity of the GEOR toward C3 products like lactate and glycerate was studied, and the reaction mechanism was discussed. The highest mass activity was found for Pt80Co20, although when the specific activity, glycerol conversion, and GEOR selectivity were compared, Pt60Co40 was the superior catalyst overall. In general, all catalysts, even those that are Co-rich, exhibited a high C3 product selectivity up to 95% at 0.67 V vs RHE. The low applied potential of 0.67 V vs RHE at 40 °C facilitated lactate formation with selectivity up to 72%. At the same time, the glycerate formation with a selectivity of up to 40%, as well as C-C bond cleavage, was more favored at 0.87 V vs RHE.

Arterial to jugular-bulb lactate difference in patients undergoing elective brain tumor craniotomy.

Hyperlactatemia is common during tumor craniotomy, but the underlying pathophysiology is unclear. This study measured simultaneous arterial and jugular-bulb lactate concentrations in patients undergoing brain tumor craniotomy to investigate the hypothesis that hyperlactatemia was associated with a net cerebrovascular lactate input. In 20 patients, arterial and jugular-bulb blood was collected hourly from the start of surgery to 6 h postoperatively for measurement of lactate, glucose, and oxygen concentration. For each marker, data were analyzed using a linear mixed-effects model with jugular-bulb concentration as dependent variable, arterial concentration as fixed effect, and patient as random effect. Furthermore, we generated regression lines between arterial and jugular-bulb concentrations. The slope of the regression line between arterial and jugular-bulb lactate was 0.95 (95% CI 0.93-0.97, R2 = 0.98), indicating that increasing arterial lactate levels were associated with an increasingly positive net cerebrovascular balance (net input). The line crossed the identity line at 2.86 (95% CI 0.57-5.16) mmol/L, indicating that lower levels of lactate were associated with a negative net cerebrovascular balance (net output). This suggests a switch from net lactate output during normolactatemia towards net input during hyperlactatemia. Hyperlactatemia in tumor-craniotomy patients probably does not originate from the brain.

Estimation of Periodontal Inflamed Surface Area by Salivary Lactate Dehydrogenase Level Using a Test Kit.

Background: Salivary lactate dehydrogenase (LD) levels are a feasible and useful parameter for screening periodontal diseases. The periodontal inflamed surface area (PISA) is useful to clinically assess periodontal diseases. However, PISA is difficult to calculate and PISA-compatible screening kits are required. We aimed to investigate the association between salivary LD levels, using a test kit, and PISA and PISA-Japanese and determine the feasibility and reliability of the salivary LD test kit for evaluation of periodontal status. Methods: This study included 110 patients (66.4% female, median and 25-75 percentiles of age were 66.5 and 53.0-75.0 years, respectively) who visited the Dental University Clinic in Japan. Resting saliva samples were collected from each participant and LD levels were evaluated in real time using a kit featuring an integer scale ranging from 1 to 10. PISA and PISA-Japanese were calculated using periodontal parameters. Results: The median salivary LD level was 4.0. The medians of PISA and PISA-Japanese were 46.9 and 61.0, respectively. Salivary LD levels were positively correlated with the bleeding on probing rate (r = 0.626, p < 0.001), PISA (r = 0.560, p < 0.001), and PISA-Japanese (r = 0.581, p < 0.001). Conclusions: Our results suggest that salivary LD levels assessed using the salivary LD kit showed a significantly positive correlation with PISA and PISA-Japanese. In addition, we developed the PISA estimation formula using salivary LD levels measured with a test kit, sex, and age.