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Independent risk factors for sepsis‐associated acute kidney injury (S‐AKI) patients include elevated lactate levels, but the specific mechanism remains unclear. Recently, An et al. discovered that excessive acetylation and inactivation of PDHA1 lead to overproduction of lactate, resulting in mitochondrial fragmentation, ATP depletion, excessive mtROS production, and mitochondrial apoptosis, thereby exacerbating AKI in sepsis. Therefore, understanding the pathophysiological processes of mitochondrial function and lactate generation in SAKI is essential and can aid in the development of novel therapeutic strategies. This review elucidates the pathological mechanisms of mitochondrial autophagy and dynamics in AKI. We also discuss the sources of lactate in SAKI and some consequences of lactonization, which may provide new strategies for improving renal injury and delaying the progression of these diseases. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Methods Results Conclusion The role of glycogen synthase kinase (GSK)‐3β in adult T‐cell leukemia (ATL) caused by human T‐cell leukemia virus type 1 (HTLV‐1) is paradoxical and enigmatic. Here, we investigated the role of GSK‐3β and its potential as a therapeutic target for ATL.Cell proliferation/survival, cell cycle, apoptosis, and reactive oxygen species (ROS) generation were examined using the WST‐8 assay, flow cytometry, and Hoechst 33342 staining, respectively. Expression of GSK‐3β and cell cycle/death‐related proteins, and survival signals was analyzed using RT‐PCR, immunofluorescence staining, and immunoblotting.HTLV‐1‐infected T‐cell lines showed nuclear accumulation of GSK‐3β. GSK‐3β knockdown and its inhibition with 9‐ING‐41 and LY2090314 suppressed cell proliferation/survival. 9‐ING‐41 induced G2/M arrest by enhancing the expression of γH2AX, p53, p21, and p27, and suppressing the expression of CDK1, cyclin A/B, and c‐Myc. It induced caspase‐mediated apoptosis by decreasing the expression of Bcl‐xL, Mcl‐1, XIAP, c‐IAP1/2, and survivin, and increasing the expression of Bak and Bax. 9‐ING‐41 also induced ferroptosis and necroptosis, promoted JNK phosphorylation, and suppressed IKKγ and JunB expression. It inhibited the phosphorylation of IκBα, Akt, and STAT3/5, induced ROS production, and reduced glycolysis‐derived lactate levels.GSK‐3β functions as an oncogene in ATL and could be a potential therapeutic target. [ABSTRACT FROM AUTHOR]

For the upcycling of waste polyethylene terephthalate (PET), encompassing both colored and fabric PET materials, we investigated the Ir(triNHC)‐catalyzed dehydrogenative coupling of PET and methanol, leading to the production of sodium lactate with good yields. We proposed a sustainable method for isolating lactic acid from the catalytic reaction mixture of sodium lactate and regenerating the base using bipolar membrane electrodialysis (BMED). This isolation method demonstrated high effectiveness, achieving isolation of lactic acid while maintaining economic feasibility at $ 0.10 per kg of lactic acid, and enabling sustainable NaOH regeneration with complete resource circulation. We assessed the recyclability of the catalyst and elucidated the mechanism involving base‐mediated depolymerization and catalyst‐promoted dehydrogenation, highlighting the importance of triNHC ligands in enhancing catalytic activity. [ABSTRACT FROM AUTHOR]

All‐inorganic cesium lead triiodide perovskites (CsPbI3) have attracted increasing attention due to their good thermal stability, remarkable optoelectronic properties, and adaptability in tandem solar cells. However, N2‐filled glovebox is generally required to strictly control the humidity during film fabrication due to the moisture‐induced black‐to‐yellow phase transition, which remains a great hinderance for further commercialization. Herein, we report an effective approach via incorporating multifunctional ethacridine lactate (EAL) to mitigate moisture invasion and enable the fabrication of efficient inverted (p‐i‐n) CsPbI3 perovskite solar cells (PSCs) under ambient condition. It is revealed that the lactate anions accelerate the crystallization of CsPbI3, shortening the exposure time to moisture during film fabrication. Meanwhile, the conjugated backbone and multiple functional groups in the ethacridine cations can interact with I− and Pb2+ to reduce the undesired defects, stabilize the perovskite structure and facilitate the charge transport in the film. Moreover, EAL incorporation also leads to better energy alignment, thus favoring charge extraction at both upper and bottom interfaces. Consequently, the device efficiency and stability are enormously enhanced, with the champion efficiency reaching 21.08 %. This even surpasses the highest value reported for the devices fabricated in glovebox, representing a record efficiency of inverted all‐inorganic PSCs. [ABSTRACT FROM AUTHOR]

Since assessing aerobic capacity is key to enhancing swimming performance, a simple and widely applicable technology should be developed. Therefore, we aimed to noninvasively visualize real‐time changes in sweat lactate (sLA) levels during swimming and investigate the relationship between lactate thresholds in sweat (sLT) and blood (bLT). This prospective study included 24 university swimmers (age: 20.7 s ± 1.8 years, 58% male) who underwent exercise tests at incremental speeds with or without breaks in a swimming flume to measure heart rate (HR), bLT, and sLT based on sLA levels using a waterproof wearable lactate sensor attached to the dorsal upper arm on two different days. The correlation coefficient and Bland–Altman methods were used to verify the similarities of the sLT with bLT and personal performance. In all tests, dynamic changes in sLA levels were continuously measured and projected onto the wearable device without delay, artifacts, or contamination. Following an initial minimal current response, with increasing speed the sLA levels increased substantially, coinciding with a continuous rise in HR. The speed at sLT strongly correlated with that at bLT (p < 0.01 and r = 0.824). The Bland–Altman plot showed a strong agreement (mean difference: 0.08 ± 0.1 m/s). This prospective study achieved real‐time sLA monitoring during swimming, even with vigorous movement. The sLT closely approximated bLT; both were subsequently validated for their relevance to performance. Highlights: A new technique using a wearable device can measure sweat lactate (sLA) levels during swimming without artifacts or contamination.Lactate threshold assessed using sLA dynamics is consistent with that calculated from blood samples.The current novel measurement method is expected to promote a personalized training regimen and simultaneous multi‐person measurements. [ABSTRACT FROM AUTHOR]

The article investigates how tumor cells use acetate to support their growth and evade the immune system. It shows that acetate is abundant in the tumor microenvironment and contributes to tumor cell proliferation and immune evasion by enhancing the acetylation of c-Myc, a key oncogenic protein. Topics include acetate's role in tumor metabolism, its impact on c-Myc acetylation and stabilization, and its effects on immune cell infiltration and tumor growth.

Purpose: In vivo quantification of lactate has numerous applications in studying the pathology of both cerebral and musculoskeletal systems. Due to its low concentration (~0.5–1 mM), and overlap with lipid signals, traditional 1H MR spectra acquired in vivo using a small voxel and short echo time often result in an inadequate signal to detect and resolve the lactate peak, especially in healthy human volunteers. Methods: In this study, using a semi‐LASER acquisition with long echo time (TE = 288 ms) and large voxel size (80 × 70 × 20 mm3), we clearly visualize the combined signal of lactate and threonine. Therefore, we call the signal at 1.33 ppm Lac+ and quantify Lac+ concentration from water suppressed spectra in healthy human brains in vivo. Four participants (22–37 years old; mean age = 28 ± 5.4; three male, one female) were scanned on four separate days, and on each day four measurements were taken. Intra‐day values are calculated for each participant by comparing the four measurements on a single day. Inter‐day values were calculated using the mean intra‐day measurements. Results: The mean intra‐participant Lac+ concentration, standard deviation (SD), and coefficient of variation (CV) ranged from 0.49 to 0.61 mM, 0.02 to 0.07 mM, and 4% to 13%, respectively, across four volunteers. The inter‐participant Lac+ concentration, SD, and CV was 0.53 mM, ±0.06 mM, and 11%. Conclusion: Repeatability is shown in Lac+ measurement in healthy human brain using a long echo time semi‐LASER sequence with a large voxel in about 3.5 min at 3 T. [ABSTRACT FROM AUTHOR]

Under hydrothermal condition, lactate derivative (R)‐4‐(1‐ carboxyethoxy)‐2‐methylbenzoic acid ((R)‐H2cma) as chiral synthon assembled with 4,4′‐di(1H‐imidazol‐1‐yl)‐1,1′‐biphenyl (4,4'‐dib) and Ni(II) ions to obtain complex {[Ni2((R)‐cma)2(4,4'‐dib)2(H2O)] ⋅ 2H2O}n (HU20‐R). In complex HU20‐R, carboxyl group from lactate unit of (R)‐cma2− anion and coordinating H2O molecule adopt a μ2‐coordination mode to obtain dinuclear [Ni2(CO2)2(H2O)]2+ cluster. (R)‐cma2− anions and Ni(II) ions build single left‐handed (R)‐cma‐Ni‐chain, while 4,4'‐dib ligands are bridged by different Ni(II) centers to form double left‐handed 4,4'‐dib‐Ni‐chain. These helical secondary structures are further connected together to result in an 8‐connected 3D framework. PXRD tests indicated that complex HU20‐R has well hydro‐stability. UV‐vis absorption experiment confirmed that HU20‐R is a semi‐conducting material with strong absorption capacity for ultraviolet‐visible (UV‐vis) light. Additionally, electrochemical experiment revealed that HU20‐R has low impedance and high charge transport capacity. Further test results confirm that HU20‐R has noticeable photo‐catalytic effect in photodegradation of Rhodamine B (RhB) and antiferromagnetic property. [ABSTRACT FROM AUTHOR]

Modulation of testing conditions such as resting lactate (Larest) levels or carbohydrate intake may affect the calculation of the maximal glycolytic rate (νLa.max). To evaluate the impact of elevated Larest as well as reduced and increased carbohydrate availability on νLa.max in running sprints (RST), twenty‐one participants completed five 15‐s RST tests on a running track under five different conditions: (I). baseline: Larest ≤1.5 mmol·L−1; (II). Lactate+: Larest ≥2.5 mmol·L−1; (III). CHO−: carbohydrate intake: ≤ 1 g·kg−1 BW d−1 for 3 days; (IV). CHO+: carbohydrate intake: ≥ 9 g·kg−1 BW d−1 for one day; and (V). acuteCHO: 500 mL glucose containing beverage consumed before RST. νLa.max was significantly reduced in lactate+ and CHO− conditions compared to the baseline RST, due to a reduction in the arithmetic mean delta (∆) between Lapeak and Larest lactate concentration (Lapeak, mmol · L−1). AcuteCHO led to an increase in Larest compared to baseline, CHO− and CHO+ with a high interindividual variability but did not significantly reduce νLa.max. Therefore, avoiding low carbohydrate nutrition before νLa.max testing, along with carefully adjusting Larest to below ≤1.5 mmol·L‐1, is crucial to prevent the unintentional underestimation of νLa.max. [ABSTRACT FROM AUTHOR]

Under the long‐term pressure overload stimulation, the heart experiences embryonic gene activation, leading to myocardial hypertrophy and ventricular remodelling, which can ultimately result in the development of heart failure. Identifying effective therapeutic targets is crucial for the prevention and treatment of myocardial hypertrophy. Histone lysine lactylation (HKla) is a novel post‐translational modification that connects cellular metabolism with epigenetic regulation. However, the specific role of HKla in pathological cardiac hypertrophy remains unclear. Our study aims to investigate whether HKla modification plays a pathogenic role in the development of cardiac hypertrophy. The results demonstrate significant expression of HKla in cardiomyocytes derived from an animal model of cardiac hypertrophy induced by transverse aortic constriction surgery, and in neonatal mouse cardiomyocytes stimulated by Ang II. Furthermore, research indicates that HKla is influenced by glucose metabolism and lactate generation, exhibiting significant phenotypic variability in response to various environmental stimuli. In vitro experiments reveal that exogenous lactate and glucose can upregulate the expression of HKla and promote cardiac hypertrophy. Conversely, inhibition of lactate production using glycolysis inhibitor (2‐DG), LDH inhibitor (oxamate) and LDHA inhibitor (GNE‐140) reduces HKla levels and inhibits the development of cardiac hypertrophy. Collectively, these findings establish a pivotal role for H3K18la in pathological cardiac hypertrophy, offering a novel target for the treatment of this condition. [ABSTRACT FROM AUTHOR]

Aim: In this study, we investigated glucose and lactate kinetics during a 75 g oral glucose tolerance test (OGTT) in 23 overweight and obese adolescents and assessed putative differences among participants with and without metabolic dysfunction‐associated steatotic liver disease (MASLD). Methods: We enrolled 23 young people (six girls) with obesity [body mass index 33 (29‐37)]. Glucose‐lactate kinetics parameters (disposal glucose insulin sensitivity, SID; fraction of glucose converted into lactate, fr; fractional lactate clearance rate, kL) and lactate production rate (LPR) were estimated using the oral glucose‐lactate minimal model. MASLD presence was assessed using the proton density fat fraction. We analysed glucose, lactate and LPR time to peak, peak values and area under the curve and evaluated differences using the Wilcoxon test. MASLD and no‐MASLD participants were compared using the Mann‐Whitney test. Correlations between parameters were assessed using the Spearman correlation coefficient (ρ). We also tested the performance of two (4 or 3 h OGTT) protocols in estimating oral glucose‐lactate minimal model and LPR parameters. Results: Glucose peaks 30 min earlier than lactate (p =.0019). This pattern was present in the no‐MASLD group (p <.001). LPR peaks 30 min later in the MASLD group (p =.02). LPR and kL were higher in MASLD, suggesting higher glycolysis and lactate utilization. SID and fr correlate significantly (ρ = −0.55, p =.008). SID and fr were also correlated with the body mass index, (ρ = −0.45, p =.04; and ρ = 0.45; p =.03). The protocol duration did not influence the estimates of the parameters. Discussion: Youth with MASLD showed a delayed glucose metabolism, possibly because of greater utilization of the underlying substrates. A 3‐h OGTT may be used to assess lactate metabolism effectively. [ABSTRACT FROM AUTHOR]

We examine the impact of the acute manipulation of oxygen availability during discrete phases (active and passive) of a repeated‐sprint cycling protocol on performance, physiological, and perceptual responses. On separate days, twelve trained males completed four sets of five 5‐s 'all out' cycle sprints (25‐s inter‐sprint recovery and 5‐min interset rest) in four randomized conditions: normobaric hypoxia (inspired oxygen fraction of 12.9%) applied continuously (C‐HYP), intermittently during only the sets of sprints (I‐HYPSPRINT) or between‐sets recovery periods (I‐HYPRECOVERY), or not at all (C‐NOR). Peak and mean power output, peripheral oxygen saturation, heart rate, blood lactate concentration, exercise‐related sensations, and vastus lateralis muscle oxygenation using near‐infrared spectroscopy were assessed. Peak and mean power output was ∼4%–5% lower for C‐HYP compared to C‐NOR (P ≤ 0.050) and I‐HYPRECOVERY (P ≤ 0.027). Peripheral oxygen saturation was lower during C‐HYP and I‐HYPSPRINT compared with C‐NOR and I‐HYPRECOVERY during sets of sprints (∼83–85 vs. ∼95%–97%; P < 0.001), while lower values were obtained for C‐HYP and I‐HYPRECOVERY than C‐NOR and I‐HYPSPRINT during between‐sets rest period (∼84–85 vs. ∼96%; P < 0.001). Difficulty in breathing was ∼21% higher for C‐HYP than C‐NOR (P = 0.050). Ratings of perceived exertion (P = 0.435), limb discomfort (P = 0.416), heart rate (P = 0.605), blood lactate concentration (P = 0.976), and muscle oxygenation‐derived variables (P = 0.056 to 0.605) did not differ between conditions. In conclusion, the method of hypoxic exposure application (continuous vs. intermittent) affects mechanical performance, while internal demands remained essentially comparable during repeated cycle sprints. Highlights: Continuous hypoxic exposure resulted in reduced repeated sprint performance compared to both normoxia and intermittent hypoxia during recoveries.Cardiovascular solicitation and glycolytic contribution showed no significant differences between ambient air and hypoxic conditions regardless of the timing of hypoxic gas administration (entire session, sprints only, or recovery only).The method of applying hypoxic exposure significantly affected mechanical performance, while internal physiological demands remained essentially comparable between conditions during repeated cycle sprints. [ABSTRACT FROM AUTHOR]

Lactate is an oncometabolite that play important role in tumor aggressiveness. Lactate from the tumor microenvironment (TME) is taken up by cancer cells as an energy resource via mitochondrial oxidative phosphorylation (or OXPHOS). In the present study, by using an online meta‐analysis tool we demonstrated that in oral squamous cancer cells (OSCCs) glycolytic and OXPHOS governing genes are overexpressed, like in breast cancer. For experimental demonstration, we treated the OSCC cell line (SCC4) and breast cancer cells (MDA‐MB‐231) with sodium L‐lactate and analyzed its effects on changes in EMT and migration. For the therapeutic intervention of lactate metabolism, we used AZD3965 (an MCT1 inhibitor), and 7ACC2 (an MPC inhibitor). Like breast cancer, oral cancer tissues showed increased transcripts of 12 genes that were previously shown to be associated with glycolysis and OXPHOS. We experimentally demonstrated that L‐lactate treatment induced mesenchymal markers and migration of cancer cells, which was significantly neutralized by MPC inhibitor that is, 7ACC2. Such an effect on EMT status was not observed with AZD3965. Furthermore, we showed that lactate treatment increases the MPC1 expression in both cancer cells, and this might be the reason why cancer cells in the high lactate environment are more sensitive to 7ACC2. Overall, our present findings demonstrate that extracellular lactate positively regulates the MPC1 protein expression in cancer cells, thereby putting forward the notion of using 7ACC2 as a potential therapeutic alternative to inhibit malignant oxidative cancers. Future preclinical studies are warranted to validate the present findings. [ABSTRACT FROM AUTHOR]

Objectives: Reflecting the need for an effective support for the daily oral hygiene routine of patients experiencing (symptoms of) gum inflammation, a new mouthwash has been developed containing an amine + zinc lactate + fluoride system. The in vitro efficacy of this product was assessed using traditional laboratory methods, as well as novel experimentation. Materials and Methods: This mouthwash has been evaluated in a series of laboratory tests including two short interval kill tests (SIKTs), a 12‐h (longer term) biofilm regrowth assay, a plaque glycolysis assay, and an aerobic, repeated exposure biofilm model, as well as tests for soft tissue uptake and LPS neutralization. Results: Several laboratory studies demonstrate that a mouthwash containing an amine + zinc lactate + fluoride system provides short‐term and long‐term antibacterial activity. While the immediate efficacy of this formula has been shown to be driven by the presence of the amine, zinc lactate provides a long‐term antibacterial effect, as well as is able to inhibit bacterial metabolism. Conclusions: This research provides the basis for understanding the mode of action of this new mouthwash formulation and explains the previously observed clinical efficacy of this formula against plaque and gingivitis. [ABSTRACT FROM AUTHOR]

Sun exposure induces major skin alterations, but its effects on skin metabolites and lipids remain largely unknown. Using an original reconstructed human epidermis (RHE) model colonized with human microbiota and supplemented with human sebum, we previously showed that a single dose of simulated solar radiation (SSR) significantly impacted the skin metabolome and microbiota. In this article, we further analyzed SSR‐induced changes on skin metabolites and lipids in the same RHE model. Among the significantly altered metabolites (log2‐fold changes with p ≤ 0.05), we found several natural moisturizing factors (NMFs): amino acids, lactate, glycerol, urocanic acid, pyrrolidone carboxylic acid and derivatives. Analyses of the stratum corneum lipids also showed that SSR induced lower levels of free fatty acids and higher levels of ceramides, cholesterols and its derivatives. An imbalance in NMFs and ceramides combined to an increase of proinflammatory lipids may participate in skin permeability barrier impairment, dehydration and inflammatory reaction to the sun. Our skin model also allowed the evaluation of an innovative ultraviolet/blue light (UV/BL) broad‐spectrum sunscreen with a high sun protection factor (SPF50+). We found that using this sunscreen prior to SSR exposure could in part prevent SSR‐induced alterations in NMFs and lipids in the skin ecosystem RHE model. [ABSTRACT FROM AUTHOR]

The high level of lactate in tumor microenvironment not only promotes tumor development and metastasis, but also induces immune escape, which often leads to failures of various tumor therapy strategies. We here report a sono‐triggered cascade lactate depletion strategy by using semiconducting polymer nanoreactors (SPNLCu) for cancer cuproptosis‐immunotherapy. The SPNLCu mainly contain a semiconducting polymer as sonosensitizer, lactate oxidase (LOx) conjugated via a reactive oxygen species (ROS)‐cleavable linker and chelated Cu2+. Upon ultrasound (US) irradiation, the semiconducting polymer generates singlet oxygen (1O2) to cut ROS‐cleavable linker to allow the release of LOx that catalyzes lactate depletion to produce hydrogen peroxide (H2O2). The Cu2+ will be reduced to Cu+ in tumor microenvironment, which reacts with the produced H2O2 to obtain hydroxyl radical (⋅OH) that further improves LOx release via destroying ROS‐cleavable linkers. As such, sono‐triggered cascade release of LOx achieves effective lactate depletion, thus relieving immunosuppressive roles of lactate. Moreover, the toxic Cu+ induces cuproptosis to cause immunogenic cell death (ICD) for activating antitumor immunological effect. SPNLCu are used to treat both subcutaneous and deep‐tissue orthotopic pancreatic cancer with observably enhanced efficacy in restricting the tumor growths. This study thus provides a precise and effective lactate depletion tactic for cancer therapy. [ABSTRACT FROM AUTHOR]

Changes in body shape are linked to swimming performance and become relevant for selective breeding programmes in cultured finfish. We studied how the selection for fast growth could affect phenotypes by investigating the relationship between swimming performance and body shape. We also investigated how swimming might affect plasma metabolite concentrations. Critical swimming speed (UCrit), body traits (e.g., BW, body weight; BL, body length; K, condition factor), and plasma lactate and glucose concentrations were evaluated in two cohorts of Australasian snapper (Chrysophrys auratus): one derived from wild broodstock (F1), and the other selected for fast growth (F4). UCrit tests (n = 8) were applied in groups of 10 snapper of similar BW (71.7 g) and BL (14.6 cm). The absolute or relative UCrit values of both cohorts were similar (0.702 m⋅s−1 and 4.795 BL⋅s−1, respectively), despite the F4 cohort displaying a higher K. A positive correlation between K and absolute UCrit (Pearson's r = 0.414) was detected in the F4 cohort, but not in the F1 cohort, which may be linked to differences in body shape. A negative correlation between relative UCrit and body size (Pearson's r between −0.682 and −0.501), but no correlation between absolute UCrit and body size, was displayed in both cohorts. Plasma lactate and glucose concentrations were higher in the F4 cohort at UCrit. Whether a longer selective breeding programme could result in more changes in body shape, potentially affecting swimming performance, should be explored, along with the potential outcomes of the differences in metabolic traits detected. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the effectiveness of a 6‐month home‐based high‐intensity interval training (HIIT) intervention to improve peak oxygen consumption (V̇O2peak) and lactate threshold (LT) in older adults. Methods: Two hundred thirty‐three healthy older adults (60–84 years; 54% females) were randomly assigned to either 6‐month, thrice‐weekly home‐based HIIT (once‐weekly circuit training and twice‐weekly interval training) or a passive control group. Exercise sessions were monitored using a Polar watch and a logbook for objective and subjective data, respectively, and guided by a personal coach. The outcomes were assessed using a modified Balke protocol combining V̇O2peak and LT measures. General linear regression models assessed between‐group differences in change and within‐group changes for each outcome. Results: There was a significant between‐group difference in the pre‐to‐post change in V̇O2peak (difference: 1.8 [1.2; 2.3] mL/kg/min; exercise: +1.4 [1.0; 1.7] mL/kg/min [~5%]; control: −0.4 [−0.8; −0.0] mL/kg/min [approximately −1.5%]; effect size [ES]: 0.35). Compared with controls, the exercise group had lower blood lactate concentration (−0.7 [−0.9; −0.4] mmol/L, ES: 0.61), % of peak heart rate (−4.4 [−5.7; −3.0], ES: 0.64), and % of V̇O2peak (−4.5 [−6.1; −2.9], ES: 0.60) at the intensity corresponding to preintervention LT and achieved a higher treadmill stage (% incline) at LT (0.6 [0.3; 0.8]; ES: 0.47), following the intervention. Conclusion: This study highlights the effectiveness of a home‐based HIIT intervention as an accessible and equipment‐minimal strategy to induce clinically meaningful improvements in cardiorespiratory fitness in older adults. Over 6 months, the exercise group showed larger improvements in all outcomes compared with the control group. Notably, the LT outcome exhibited a more pronounced magnitude of change than V̇O2peak. [ABSTRACT FROM AUTHOR]

Conventional farming practices have negatively impacted micronutrient fertility and overall soil health. Metal lactates are an organic micronutrient amendment that provide both a labile carbon substrate as well as mineral nutrition for plant and microbial growth. To determine the ability of metal lactates to provide readily available micronutrients, Zn, Cu, Mn, Ni, and Co in lactate and chloride salt form were amended to soils and incubated for 28 days. Operationally defined speciation was determined using sequential extraction on samples incubated for 1, 5, or 28 days. The results show a comparable distribution of metals in chloride and lactate form; however, differences were detected in water‐soluble and exchangeable Ni and Zn at each timepoint. For example, in the water exchangeable fraction, there was 2.6%–2.9% less Ni and 0.2%–0.3% less Zn in the metal lactate‐treated soil compared to soil treated with metal chlorides. Furthermore, carbonate‐bound Ni averaged 4.1% and 4% less in metal lactate‐treated soils as compared to metal chloride‐treated soils on days 1 and 5, and Cu decreased 2.9%–3.3% during the treatment period for the lactate‐bound form. Additionally, microbial phospholipid fatty acid (PLFA) was performed and found a stimulatory effect of metal lactates on bacterial biomass with an increase of 12%–18% relative to the metal chloride treatment. Results from this study support the use of metal lactates as a sustainable alternative to conventional fertilizers by providing bioavailable micronutrients for plant nutrition in addition to a labile carbon source to support the growth of microbial populations. Core Ideas: Zn, Cu, Ni, and Co in lactate and chloride salt form have similar distribution in silt loam soil.Zn, Cu, and Ni supplied in chloride form were significantly more available than lactate forms.Metal lactates led to significantly greater bacterial and protozoan biomass compared to metal chlorides. [ABSTRACT FROM AUTHOR]

Understanding how animals respond to stressors is critical for effective conservation. The present study aimed to evaluate the physiological recovery of the Shortnose Guitarfish, Zapteryx brevirostris after being incidentally captured by artisanal fleets and compared it to guitarfish with delayed mortality. Moreover, the study aimed to test the efficiency of a rehabilitation protocol for the species. To this end, individuals landed alive were transported to the rehabilitation facilities and kept in tanks under monitoring for 3 days. Physiological markers indicative of allostatic overload (i.e., lactate and phosphorus) and energy metabolism (i.e., glucose and β‐hydroxybutyrate) were assessed in the serum of the studied guitarfish: right after gillnet capture (i.e., post‐capture) and on rehabilitation (i.e., pre‐monitoring, post‐monitoring, as well as guitarfish that deceased during monitoring – post‐mortem). Results showed that the transportation and additional handling employed in the rehabilitation protocol did not increase the stress response, pointing to its potential efficacy in recovering debilitated, incidentally caught guitarfish before release. As for recovery success of monitored guitarfish, lactic acidosis was fully reverted after a 3‐day rest period, as was allostatic overload. The same was not observed in recovery failure. Correlation tests revealed key relationships between physiological markers, shedding light on how physiological pathways help guitarfish cope with capture and handling stress. This study highlights the valuable application of conservation physiology principles to fisheries management of this endemic and threatened guitarfish species. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study is to measure staff compliance with the local umbilical cord lactate (UCL) sampling guideline and investigate the quality of paired UCG samples at a tertiary maternity unit. Methods: We performed a retrospective consecutive sampling of 100 babies delivered via emergency caesarean section and 50 babies with each of all other guideline‐based indications for UCL sampling born on and before 31 December 2021. Data were extracted from physical and electronic records. Compliance with guideline‐based indications for UCL at birth was measured. The proportion of valid UCG samples was calculated. Samples were considered invalid under the following cases: (i) inadvertently collecting from the same vessel, (ii) switching arterial and venous samples, (iii) collecting from only one vessel or (iv) committing errors during sample collection and handling. Results: Of the samples collected at birth from 321 babies, 280 (87%) had UCL. Small for gestational age and concerns about fetal well‐being in labour were indications associated with poorer compliance, 66% and 78%, respectively. About 99 (44%) babies of 226 babies with UCG performed had valid UCG samples. The most common reasons for invalid samples were collection and handling errors (22%) and inadvertent collection from the same vessel (15%). Conclusions: Generally, compliance with the guidelines is good. However, invalid UCG samples were more frequent than expected. [ABSTRACT FROM AUTHOR]

To investigate the effect of forced even pacing through virtual pacing assistance and an opponent in a competitive setting on end‐spurt behaviour in freestyle swimmers, including related physiological underpinnings. Twenty‐seven competitive swimmers and triathletes were recruited. There were four 1500 m freestyle trials: (i) familiarisation time trial, (ii) self‐paced time trial (STT), (iii) head‐to‐head competition time trial (CTT) and (iv) forced even pacing through virtual pacing assistance time trial (FET). Eventually, 12 swimmers met the criteria for the CTT and FET to be included in the analysis. Changes in end‐spurt behaviour, finishing time and physiological parameters (lactate, cortisol, noradrenaline and heart rate) were analysed using a linear mixed model with fixed effects for trials and a random effect for swimmer identity. A separate linear model was computed for competition outcome. The end‐spurt for each race was determined by means of an end‐spurt indicator (ESI; ESI > 0 greater end‐spurt). Swimmers demonstrated a significantly greater ESI in FET (+2.6; p < 0.001) and CTT (+1.4; p = 0.022) compared to STT. Blood lactate concentration in FET (+1.0 mmol L−1; p < 0.001) and CTT (+1.6 mmol L−1; p < 0.001) was significantly higher than in STT. Winners had a significantly greater ESI than losers in CTT (+1.6 and p = 0.005). Swimmers utilised a greater end‐spurt through metabolically optimal forced even pacing by virtual pacing assistance and in a head‐to‐head competition due a larger mobilisation of anaerobic reserves as indicated by greater blood lactate concentrations. Winners had a significantly greater end‐spurt than losers despite similar metabolic disturbances. Highlights: Compared to a self‐paced time trial, swimmers in a forced even pacing trial by virtual pacing assistance and in a head‐to‐head competition execute a greater end‐spurt.The larger end‐spurt is associated with larger mobilisation of anaerobic reserves as indicated by greater blood lactate concentrations.Winners had a significantly greater end‐spurt than losers despite similar metabolic disturbances. [ABSTRACT FROM AUTHOR]

Citrulline malate (CM) is purported to be an ergogenic aid during various types of exercise performance. However, the effects of CM on repeated sprint performance (RSP) are under‐explored. In a placebo‐controlled, double‐blind, counterbalanced cross‐over design, male university‐level team sport athletes (n = 13) performed two familiarization trials, after which CM or placebo (PLA) (8 × 1 g tablets each day) were taken on the 2 days prior to, and with breakfast on the morning of, each main experimental trial. The main experimental trials employed a RSP protocol consisting of 10 repetitions of 40 m maximal shuttle run test (MST) with a 30 s interval between the start of each sprint. Sprint times and heart rate were recorded throughout the MST, and blood lactate concentrations were measured before, immediately after, and 5 min after completing the MST. CM resulted in better RSP compared to PLA, as indicated by a lower sprint performance decrement (Sdec: CM, 4.68% ± 1.82% vs. PLA, 6.10% ± 1.83%; p = 0.03; ES = 0.77), which was possibly influenced by the fastest sprint time being faster in CM (CM, 8.16 ± 0.34 s vs. PLA, 8.29 ± 0.39 s; p = 0.011; ES = 0.34). There were no differences between CM and PLA in average sprint time (p = 0.54), slowest sprint time (p = 0.48), blood lactate concentrations (p = 0.73) or heart rate (p = 0.18), nor was there a condition × time interaction effect across the 10 sprints (p = 0.166). Three days of CM supplementation (8 g daily) attenuated the sprint performance decrement during short‐duration high‐intensity exercise in the form of running RSP in male university‐level team sport athletes. Highlights: This study addresses a knowledge gap around the ergogenic potential of citrulline malate (CM) in repeated sprint running performance.Three days of CM supplementation (8 g daily) was observed to improve short‐duration (5 min) high‐intensity exercise performance in male university‐level team sport athletes when measured by the sprint performance decrement in a 10 repetition 40 m maximal shuttle run test.The attenuation in the sprint performance decrement was not associated with any differences compared to the placebo condition in heart rate or blood lactate concentrations.The outcomes of this study suggest that short‐term CM supplementation could be beneficial for team sport athletes who perform short‐duration high‐intensity efforts, such as soccer, Gaelic games, field hockey, and rugby. [ABSTRACT FROM AUTHOR]

We investigated the effect of ischemic preconditioning (IPC) with and without caffeine supplementation on mean power output (MPO) during a 4‐min cycling time‐trial (TT). In a double‐blinded, randomized, crossover‐design, 11 trained men performed a TT on 4 days separated by ∼1 week. One hour before TT, participants ingested either caffeine (3 mg kg bw−1) or placebo pills, after which femoral blood‐flow was either restricted with occlusion cuffs inflated to ∼180 mmHg (IPC), or sham‐restricted (0–10 mmHg; Sham) during 3 × 2‐min low‐intensity cycling (10% of incremental peak power output). Then, participants performed a standardized warm‐up followed by the TT. Plasma lactate and K+ concentrations and ratings of perceived exertion (RPE) were measured throughout trials. TT MPO was 382 ± 17 W in Placebo + Sham and not different from Placebo + IPC (−1 W; 95% CI: −9 to 7; p = 0.848; d: 0.06), whereas MPO was higher with Caffeine + Sham (+6W; 95% CI: −2 to 14; p = 0.115; d: 0.49) and Caffeine + IPC (+8 W; 95% CI: 2–13; p = 0.019; d: 0.79) versus Placebo + Sham. MPO differences were attributed to caffeine (caffeine main‐effect: +7 W; 95% CI: 2–13; p = 0.015; d: 0.54. IPC main‐effect: 0 W; 95% CI: −6 to 7; p = 0.891; d: 0.03; caffeine × IPC interaction‐effect: p = 0.580; d: 0.17). TT RPE and plasma variables were not different between treatments. In conlcusion, IPC with co‐ingestion of placebo does not improve short‐term high‐intensity performance in trained men versus a double‐placebo control (Placebo + Sham) and does not additively enhance performance with caffeine. These data do not support IPC as a useful strategy for athletes prior to competition but confirms caffeine's performance‐enhancing effect. Highlights: Active ischemic preconditioning (IPC) prior to exercise has been proposed as a strategy to enhance short‐term exercise performance.However, the effect of combined IPC and caffeine ingestion on short‐term high‐intensity exercise performance in trained individuals remains unclear.Active IPC with co‐ingestion of placebo pills did not improve short‐term high‐intensity exercise performance in trained men and its use cannot be recommended over caffeine to improve subsequent short‐term maximal performanceIngestion of caffeine (3 mg kg bw−1) prior to short‐term high‐intensity exercise is an effective ergogenic strategy which athletes may benefit from. [ABSTRACT FROM AUTHOR]

This manuscript presents a comprehensive investigation into the role of lactate metabolism‐related genes as potential prognostic markers in skin cutaneous melanoma (SKCM). Bulk‐transcriptome data from The Cancer Genome Atlas (TCGA) and GSE19234, GSE22153, and GSE65904 cohorts from GEO database were processed and harmonized to mitigate batch effects. Lactate metabolism scores were assigned to individual cells using the 'AUCell' package. Weighted Co‐expression Network Analysis (WGCNA) was employed to identify gene modules correlated with lactate metabolism. Machine learning algorithms were applied to construct a prognostic model, and its performance was evaluated in multiple cohorts. Immune correlation, mutation analysis, and enrichment analysis were conducted to further characterize the prognostic model's biological implications. Finally, the function of key gene NDUFS7 was verified by cell experiments. Machine learning resulted in an optimal prognostic model, demonstrating significant prognostic value across various cohorts. In the different cohorts, the high‐risk group showed a poor prognosis. Immune analysis indicated differences in immune cell infiltration and checkpoint gene expression between risk groups. Mutation analysis identified genes with high mutation loads in SKCM. Enrichment analysis unveiled enriched pathways and biological processes in high‐risk SKCM patients. NDUFS7 was found to be a hub gene in the protein–protein interaction network. After the expression of NDUFS7 was reduced by siRNA knockdown, CCK‐8, colony formation, transwell and wound healing tests showed that the activity, proliferation and migration of A375 and WM115 cell lines were significantly decreased. This study offers insights into the prognostic significance of lactate metabolism‐related genes in SKCM. [ABSTRACT FROM AUTHOR]

Schizophrenia (SCZ) is a complex neuropsychiatric disorder widely recognized for its impaired bioenergy utilization. The astrocyte‐neuron lactate shuttle (ANLS) plays a critical role in brain energy supply. Recent studies have revealed abnormal lactate metabolism in SCZ, which is associated with mitochondrial dysfunction, tissue hypoxia, gastric acid retention, oxidative stress, neuroinflammation, abnormal brain iron metabolism, cerebral white matter hypermetabolic activity, and genetic susceptibility. Furthermore, astrocytes, neurons, and glutamate abnormalities are prevalent in SCZ with abnormal lactate metabolism, which are essential components for maintaining ANLS in the brain. Therefore, an in‐depth study of the pathophysiological mechanisms of ANLS in SCZ with abnormal lactate metabolism will contribute to a better understanding of the pathogenesis of SCZ and provide new ideas and approaches for the diagnosis and treatment of SCZ. [ABSTRACT FROM AUTHOR]

In this paper, we consider a singular nonlinear differential system that characterizes the intricate dynamics of brain lactate kinetics between cells and capillaries, as described by System (1.1) below. We begin by establishing the existence and uniqueness of nonnegative solutions for our system through the application of Schauder's fixed-point theorem. Subsequently, we explore the behavior of these solutions as the viscosity term approaches zero, shedding light on the system's dynamic evolution in such scenarios. To provide empirical validation for our theoretical findings, we offer a series of numerical simulations. These simulations not only confirm the results we have obtained but also reinforce prior research, underscoring the model's efficiency in capturing the complexities of the brain's lactate kinetics. Our work contributes not only to the theoretical underpinning of this field but also to its practical implications, making it a valuable resource for both researchers and practitioners seeking to comprehend and manipulate these vital biological processes. [ABSTRACT FROM AUTHOR]

The human gut hosts numerous ecological niches for microbe–microbe and host–microbe interactions. Gut lactate homeostasis in humans is crucial and relies on various bacteria. Veillonella spp., gut lactate‐utilizing bacteria, and lactate‐producing bacteria were frequently co‐isolated. A recent clinical trial has revealed that lactate‐producing bacteria in humans cross‐feed lactate to Veillonella spp.; however, their interspecies interaction mechanisms remain unclear. Veillonella dispar, an obligate anaerobe commonly found in the human gut and oral cavity, ferments lactate into acetate and propionate. In our study, we investigated the interaction between V. dispar ATCC 17748T and three representative phylogenetically distant strains of lactic acid bacteria, Lactobacillus acidophilus ATCC 4356T, Lacticaseibacillus paracasei subsp. paracasei ATCC 27216T, and Lactiplantibacillus plantarum ATCC 10241. Bacterial growth, viability, metabolism and gene level adaptations during bacterial interaction were examined. V. dispar exhibited the highest degree of mutualism with L. acidophilus. During co‐culture of V. dispar with L. acidophilus, both bacteria exhibited enhanced growth and increased viability. V. dispar demonstrated an upregulation of amino acid biosynthesis pathways and the aspartate catabolic pathway. L. acidophilus also showed a considerable number of upregulated genes related to growth and lactate fermentation. Our results support that V. dispar is able to enhance the fermentative capability of L. acidophilus by presumably consuming the produced lactate, and that L. acidophilus cross‐feed not only lactate, but also glutamate, to V. dispar during co‐culture. The cross‐fed glutamate enters the central carbon metabolism in V. dispar. These findings highlight an intricate metabolic relationship characterized by cross‐feeding of lactate and glutamate in parallel with considerable gene regulation within both L. acidophilus (lactate‐producing) and V. dispar (lactate‐utilizing). The mechanisms of mutualistic interactions between a traditional probiotic bacterium and a potential next‐generation probiotic bacterium were elucidated in the production of short‐chain fatty acids. [ABSTRACT FROM AUTHOR]

During prolonged running at moderate‐to‐high intensity, running economy (RE) deteriorates and attainable maximal oxygen consumption (VO2max) decreases. Whether these changes appear similarly in trained and untrained runners exercising at the same relative intensity is not clear. We recruited 10 trained runners (TR) and 10 active adults (AA), and compared RE and attainable VO2max before and after 1 h of running at 70% of VO2max. Submaximal VO2 increased more (p = 0.019) in AA (0.20 ± 0.13 L min−1) than in TR (0.07 ± 0.05 L min−1). Attainable VO2max decreased in AA (−0.21 ± 0.15 L min−1, p = 0.002), but remained unchanged in TR (−0.05 ± 0.10 L min−1, p = 0.18). Relative intensity (i.e., VO2/attainable VO2max), increased more (p = 0.001) in AA (8.3 ± 4.4%) than in TR (2.6 ± 1.9%). These results demonstrate that the ability to resist changes in RE and VO2max following prolonged running is superior in trained versus untrained runners, when exercising at the same relative intensity. [ABSTRACT FROM AUTHOR]

Lactate shuttled from the blood circulation, astrocytes, oligodendrocytes or even activated microglia (resident macrophages) to neurons has been hypothesized to represent a major source of pyruvate compared to what is normally produced endogenously by neuronal glucose metabolism. However, the role of lactate oxidation in fueling neuronal signaling associated with complex cortex function, such as perception, motor activity, and memory formation, is widely unclear. This issue has been experimentally addressed using electrophysiology in hippocampal slice preparations (ex vivo) that permit the induction of different neural network activation states by electrical stimulation, optogenetic tools or receptor ligand application. Collectively, these studies suggest that lactate in the absence of glucose (lactate only) impairs gamma (30–70 Hz) and theta-gamma oscillations, which feature high energy demand revealed by the cerebral metabolic rate of oxygen (CMRO2, set to 100%). The impairment comprises oscillation attenuation or moderate neural bursts (excitation–inhibition imbalance). The bursting is suppressed by elevating the glucose fraction in energy substrate supply. By contrast, lactate can retain certain electric stimulus-induced neural population responses and intermittent sharp wave-ripple activity that features lower energy expenditure (CMRO2 of about 65%). Lactate utilization increases the oxygen consumption by about 9% during sharp wave-ripples reflecting enhanced adenosine-5′- triphosphate (ATP) synthesis by oxidative phosphorylation in mitochondria. Moreover, lactate attenuates neurotransmission in glutamatergic pyramidal cells and fast-spiking, γ-aminobutyric acid (GABA)ergic interneurons by reducing neurotransmitter release from presynaptic terminals. By contrast, the generation and propagation of action potentials in the axon is regular. In conclusion, lactate is less effective than glucose and potentially detrimental during neural network rhythms featuring high energetic costs, likely through the lack of some obligatory ATP synthesis by aerobic glycolysis at excitatory and inhibitory synapses. High lactate/glucose ratios might contribute to central fatigue, cognitive impairment, and epileptic seizures partially seen, for instance, during exhaustive physical exercise, hypoglycemia and neuroinflammation. [ABSTRACT FROM AUTHOR]

Isotopic assays of brain glucose utilization rates have been used for more than four decades to establish relationships between energetics, functional activity, and neurotransmitter cycling. Limitations of these methods include the relatively long time (1–60 min) for the determination of labeled metabolite levels and the lack of cellular resolution. Identification and quantification of fuels for neurons and astrocytes that support activation and higher brain functions are a major, unresolved issues. Glycolysis is preferentially up-regulated during activation even though oxygen level and supply are adequate, causing lactate concentrations to quickly rise during alerting, sensory processing, cognitive tasks, and memory consolidation. However, the fate of lactate (rapid release from brain or cell–cell shuttling coupled with local oxidation) is long disputed. Genetically encoded biosensors can determine intracellular metabolite concentrations and report real-time lactate level responses to sensory, behavioral, and biochemical challenges at the cellular level. Kinetics and time courses of cellular lactate concentration changes are informative, but accurate biosensor calibration is required for quantitative comparisons of lactate levels in astrocytes and neurons. An in vivo calibration procedure for the Laconic lactate biosensor involves intracellular lactate depletion by intravenous pyruvate-mediated trans-acceleration of lactate efflux followed by sensor saturation by intravenous infusion of high doses of lactate plus ammonium chloride. In the present paper, the validity of this procedure is questioned because rapid lactate–pyruvate interconversion in blood, preferential neuronal oxidation of both monocarboxylates, on-going glycolytic metabolism, and cellular volumes were not taken into account. Calibration pitfalls for the Laconic lactate biosensor also apply to other metabolite biosensors that are standardized in vivo by infusion of substrates that can be metabolized in peripheral tissues. We discuss how technical shortcomings negate the conclusion that Laconic sensor calibrations support the existence of an in vivo astrocyte–neuron lactate concentration gradient linked to lactate shuttling from astrocytes to neurons to fuel neuronal activity. [ABSTRACT FROM AUTHOR]

Heart Rate (HR) is widely used for erobic exercise intensity prescriptions and/or studies of exercise training. It is often assumed that exercising at a given HR results in similar physiological response, regardless of exercise modality. This study aimed to gauge cellular immune mobilization to submaximal exercise at a given target HR on a cycle ergometer (CE) and treadmill (TM). Thirteen healthy male adults (23.2 ± 3.5 y.o) completed 4 laboratory visits. Participants performed two graded exercise tests to exhaustion on CE and TM and two 30‐min constant exercise challenges at 70% HR reserve on CE or TM in random order. Rating of Perceived Exertion (RPE) was recorded every 5 min, and blood was drawn before and after exercise to measure leukocytes subpopulation levels, lactate, and IL‐6. HR was successfully "clamped" during the exercise in CE and TM (CE 156.7 ± 1.1; TM 159.3 ± 1.6 bpm). Cycling was perceived as more strenuous than running and was accompanied by a greater increase in lactate post‐exercise (p < 0.0001; 6.2 ± 0.3 vs. 2.9 ± 0.3 mmol/L). IL‐6 and leukocytes subpopulations were significantly elevated post‐exercise (p < 0.003) with no difference between exercise modalities (monocytes; CE 57.6% TM 61.2%, granulocytes; CE 41.37%, TM 50.1%, lymphocytes; CE 91.03%, TM 78.8%). The findings revealed that HR is not sufficient in and of itself to fully assess the metabolic stress associated with a given exercise modality. However, despite different metabolic and subjective stress, the IL‐6 and leukocyte counts relative changes were similar in the two modalities. Highlights: These findings provide valuable insights into the leukocytes and lactate responses to cycling and running at the same target heart rate. The study further elaborates on the shared patterns and distinctions in physiological and metabolic responses and their implications for designing targeted training programs.At the same target heart rate, running resulted in significantly lower lactate levels and subjective rate of perceived exertion (RPE) while yielding higher VO2 levels compared to cycling.Leukocytes and IL‐6 increases post‐exercise were not different between running and cycling, indicating that they did not reflect the distinct metabolic and subjective perceived loads associated with cycling and running.Since heart rate in and of itself is not sufficient to fully characterize the metabolic stress induced by a specific exercise modality, it is important to consider the modality of exercise when prescribing training programs for improving cardiovascular fitness or achieving target energy expenditure through heart rate monitoring. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is one of the most common gynecological cancers. Accumulated evidence shows that long non‐coding RNAs (lncRNAs) play essential roles in cervical cancer occurrence and progression, but their specific functions and mechanisms remain to be further explored. Methods: The RT‐qPCR assay was used to detect the expression of NEAT1 in cervical cancer tissues and cell lines. CCK‐8, colony formation, flow cytometry, western blotting, and Transwell assays were used to evaluate the impact of NEAT1 on the malignant behavior of cervical cancer cells. Glucose consumption, lactate production, ATP levels, ROS levels, MMP levels, and the mRNA expressions of glycolysis‐related genes and tricarboxylic acid cycle‐related genes were detected to analyze the effect of NEAT1 on metabolism reprograming in cervical cancer cells. The expressions of PDK1, β‐catenin and downstream molecules of the WNT/β‐catenin signaling pathway in cervical cancer cells and tissues were detected by western blotting, RT‐qPCR, immunofluorescence and immunohistochemistry assays. Results: This study investigated the role and possible molecular mechanism of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in cervical cancer. Our results showed that NEAT1 was highly expressed in cervical cancer tissues and cell lines. Downregulation of NEAT1 inhibited the proliferation, migration, invasion and glycolysis of cervical cancer cells, while overexpression of NEAT1 led to the opposite effects. Mechanistically, NEAT1 upregulated pyruvate dehydrogenase kinase (PDK1) through the WNT/β‐catenin signaling pathway, which enhanced glycolysis and then facilitated cervical cancer metastasis. Furthermore, NEAT1 maintained the protein stability of β‐catenin but did not affect its mRNA level. We also excluded the direct binding of NEAT1 to the β‐catenin protein via RNA pull‐down assay. The suppressive impact of NEAT1 knockdown on cell proliferation, invasion, and migration was rescued by β‐catenin overexpression. The WNT inhibitor iCRT3 attenuated the carcinogenic effect induced by NEAT1 overexpression. Conclusion: In summary, these findings indicated that NEAT1 may contribute to the progression of cervical cancer by activating the WNT/β‐catenin/PDK1 signaling axis. [ABSTRACT FROM AUTHOR]

A unique feature of the tumor microenvironment is extracellular acidosis in relation to intracellular milieu. Metabolic reprogramming in tumors results in overproduction of H+ ions (and lactate), which are extruded from the cells to support tumor survival and progression. As a result, the transmembrane pH gradient (ΔpH), representing the difference between intracellular pH (pHi) and extracellular pH (pHe), is posited to be larger in tumors compared with normal tissue. Controlling the transmembrane pH difference has promise as a potential therapeutic target in cancer as it plays an important role in regulating drug delivery into cells. The current study shows successful development of an MRI/MRSI‐based technique that provides ΔpH imaging at submillimeter resolution. We applied this technique to image ΔpH in rat brains with RG2 and U87 gliomas, as well as in mouse brains with GL261 gliomas. pHi was measured with Amine and Amide Concentration‐Independent Detection (AACID), while pHe was measured with Biosensor Imaging of Redundant Deviation in Shifts (BIRDS). The results indicate that pHi was slightly higher in tumors (7.40–7.43 in rats, 7.39–7.47 in mice) compared with normal brain (7.30–7.38 in rats, 7.32–7.36 in mice), while pHe was significantly lower in tumors (6.62–6.76 in rats, 6.74–6.84 in mice) compared with normal tissue (7.17–7.22 in rats, 7.20–7.21 in mice). As a result, ΔpH was higher in tumors (0.64–0.81 in rats, 0.62–0.65 in mice) compared with normal brain (0.13–0.16 in rats, 0.13–0.16 in mice). This work establishes an MRI/MRSI‐based platform for ΔpH imaging at submillimeter resolution in gliomas. [ABSTRACT FROM AUTHOR]

Lactate accumulated in Tumor is a key oncometabolite and associated with various oncogenic processes, including proliferation, invasion, angiogenesis, metastasis, immunosuppression and therapeutic resistance. Particularly, lactate contributes to the apoptosis and ferroptosis resistance in cancer cells. Consequently, blockade of lactate provides a promising opportunity for cancer therapy. However, due to abnormal tumor microenvironment (TME) and intracellular glutathione (GSH) mediated ferroptosis resistance, the current approaches for regulating lactate to sensitize cells to apoptosis and ferroptosis are still challenging. Herein, we developed a catalytic lactate oxidizing liposomes (Lip‐LM) incorporated with lactate oxidase (LOX)‐loaded MnO2 nanoparticles. O2 regenerated from H2O2 constitute closed‐loop of lactate oxidation catalyzed by LOX, enhancing the lactate‐consuming efficacy in TME. Besides, glutathione is consumed by MnO2 to amplify the ferroptosis susceptibility of cancer cells. The results showed that Lip‐LM achieved synergistical apoptosis and ferroptosis to enhance the anti‐tumor efficacy of amplified oxidative stress in cancer cells through the strategy of self‐sufficient O2 supplying and GSH consumption. The results of transcriptomics and proteomics analyses also support the synergistical anti‐tumor mechanisms of Lip‐LM. Hence, it is a promising catalytic nanoplatform combined lactate regulation and oxidative stress amplification and have great potential to further enhance therapeutic outcomes based on synergistical apoptosis and ferroptosis. [ABSTRACT FROM AUTHOR]

Chronic wound monitoring can provide personalized pathophysiological information for wound management and treatment. Continuously monitoring the wound milieu via the holographic pH sensor can reflect the wound healing processes. However, the integration with wearable devices is hindered by its inherently restricted interrogation angle dependency within 5°. Herein, a ball bearing‐based double photopolymerization method is developed to fabricate holographic pH sensors with a broader interrogation angle range of 15°–60° in wound exudates. The fabricated holographic pH sensor is then integrated with the flexible ultrathin polyurethane substrate, which replays a total Bragg peak shift of approximately 150 nm with physiological pH changes from 7.00 to 8.75. The conformable holographic pH sensing bandages demonstrate the ability to quantify the pH value under various bending manipulations, simulating the mounting on the body surface. The reversibility in artificial wound exudate demonstrates the durability and capability of real‐time pH monitoring in the wound milieu with minimal effect on the replay wavelength. The addition of electrolytes, albumin, urea, uric acid, lactate, and glucose does not interfere with the readout over the physiological pH range of wound exudates. The obtained conformable holographic sensing bandage benefits the wound healing process monitoring through colorimetric interrogation at point‐of‐care (POC) settings. [ABSTRACT FROM AUTHOR]

Lactate is now considered an additional fuel or signaling molecule in the brain. In this study, using an oxygen–glucose deprivation (OGD) model, we found that treatment with lactate inhibited the global increase in intracellular calcium ion concentration ([Ca2+]) in neurons and astrocytes, decreased the percentage of dying cells, and caused a metabolic shift in astrocytes and neurons toward aerobic oxidation of substrates. OGD resulted in proinflammatory changes and increased expression of cytokines and chemokines, whereas incubation with lactate reduced these changes. Pure astrocyte cultures were less sensitive than neuroglia cultures during OGD. Astrocytes exposed to lipopolysaccharide (LPS) also showed pro‐inflammatory changes that were reduced by incubation with lactate. Our study suggests that lactate may have neuroprotective effects under ischemic and inflammatory conditions. [ABSTRACT FROM AUTHOR]

Aim: To evaluate umbilical arterial lactate concentrations after spontaneous vaginal delivery and after elective Cesarean delivery, and to study the simultaneous effects of maternal and obstetric variables in high lactate levels in vaginally delivered healthy term singletons. Methods: The birth register study included information about the umbilical artery lactate values and clinical perinatal data from 7723 women and their singleton newborns (7301 spontaneous vaginal and 422 elective cesareans) from Kuopio University Hospital, Finland. High lactate levels were evaluated more extensively among healthy term neonates (N = 6541), to evaluate high levels after normal vaginal labors. Results: The mean lactate level was significantly lower after elective cesarean compared to vaginal delivery (2.42 [0.94] vs. 3.56 [1.62] mmol/l; p < 0.0001). Consequently, the 90th percentile limit values were 3.60 and 5.80 mmol/L. Among healthy term newborns born vaginally, higher lactate values (≥5.80 mmol/L) were independently associated with a longer duration of the active second stage of labor (ORs 1.91–10.97) and duration of ruptured fetal membranes (ORs 1.36–2.46), higher gestational age at birth (ORs 1.41–1.86), null parity (OR 2.17), maternal infection (OR 1.81) and short maternal stature (OR 1.45). We report 90th/95th limits for umbilical arterial lactate values in relation to the various durations of labors for term newborns who are delivered by the vaginal route. Conclusions: Even though the high umbilical lactate levels may indicate serious birth asphyxia, levels after vaginal birth reflect the physiological stress and subclinical transient asphyxia frequently seen in normal vaginal deliveries. [ABSTRACT FROM AUTHOR]

This study compared physiological and perceptual responses between cycling prescribed using fixed‐power (PWR) and fixed rating of perceived exertion (RPE), when performed with blood flow restricted (BFRPWR and BFRRPE) and unrestricted (CONPWR and CONRPE). Endurance cyclists/triathletes cycled for 10 min in four separate randomized conditions; that is, two methods of prescribed exercise intensity (power at the first ventilatory threshold or RPE matched to CONPWR) combined with two occlusion levels (with BFR or without). Cardiorespiratory and perceptual variables were recorded every 2 min. Blood lactate concentration was measured pre‐, immediately and 2‐min postexercise. Power output during BFRRPE was lower than CONRPE (−13 ± 13%). The greatest physiological and perceptual responses were achieved during BFRPWR. Heart rate during BFRRPE was not different compared with CONPWR, yet was greater than CONRPE (+4 ± 11%). Muscular discomfort during BFRRPE was greater than CONPWR (+43 ± 18%) and CONRPE (+65 ± 58%). Cuff pain was greater during BFRPWR than BFRRPE (+14 ± 21%). Blood lactate concentration was not different between BFRRPE, CONPWR, and CONRPE at any timepoint. The reduction in power (fixed‐RPE trials; BFR minus unrestricted) correlated with changes in the respiratory rate (r = 0.85, confidence intervals [CI] = 0.51, 0.96) and postexercise lactate (r = 0.75, CI = 0.27, 0.93) but not muscular discomfort (r = 0.18, CI = −0.47, 0.71). Cardiorespiratory and metabolic stress, muscular discomfort, and cuff pain likely mediated self‐regulating fixed‐RPE cycling with BFR. While cycling with BFR at a fixed‐RPE resulted in less physiological stress compared to BFRPWR, it still provided a heightened level of physiological stress, with less pain and discomfort. As such, fixed‐RPE can be a suitable alternative for prescribing BFR to trained cyclists. Highlights: Applying BFR at the fixed‐power associated with the first ventilatory threshold can increase the heart rate from the moderate to high exercise intensity domain for some individuals, indicating BFR exercise may not necessarily be low intensity.Fixed‐power cycling with BFR can be used at low work rates, perhaps following injury, yet practitioners should consider the balance between the physiological demands, discomfort, and pain at any given work rate.Discomfort and pain associated with BFR is alleviated in a fixed‐RPE model, which presents a suitable method of prescribing aerobic BFR cycling, yet physiological stress is lower compared to BFR cycling at a fixed‐power. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is a common malignancy which threatens the health of women. Circular RNAs (circRNAs) are critical factors in multiple cancers, including BC. The aim of this experiment was to investigate the molecular mechanisms of circRNA Septin 9 (circSEPT9) in the progression of BC. Methods: CircSEPT9, microRNA-625-5p (miR-625-5p) and polypyrimidine tractbinding protein 3 (PTBP3) levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was performed to detect the protein levels of PTBP3, E-cadherin and vimentin. Cell counting kit-8 assay (CCK8) and thymidine analog 5-ethynyl-20-deoxyuridine (EDU) was utilized for proliferation examination. Flow cytometry was conducted to measure apoptosis. Transwell assay and wound healing assay to investigate the migration of BC cells. Glucose uptake and lactate production were determined by specific kits. Additionally, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were utilized to verify the interaction. A murine xenograft model was established to investigate the function of circSEPT9 in BC in vivo. Results: Overexpression of circSEPT9 was found in BC tissues and cells. Silencing circSEPT9 impeded BC cell proliferation, migration, epithelial-mesenchymal transition (EMT) and glycolytic metabolism but facilitated cell apoptosis in vitro. Meanwhile, circSEPT9 knockdown constrained tumor growth in vivo. MiR-625-5p was targeted by circSEPT9. The influence of silencing circSEPT9 on BC cell function was regained by miR-625-5p inhibitor. Furthermore, miR-625-5p regulated BC cell malignant phenotypes via downregulating PTBP3. Conclusion: circSEPT9 contributed to the malignant progression of BC by upregulating PTBP3 via sponging miR-625-5p. [ABSTRACT FROM AUTHOR]

Dysregulated macrophage responses and changes in tissue metabolism are hallmarks of chronic inflammation in the skin. However, the metabolic cues that direct and support macrophage functions in the skin are poorly understood. Here, we show that during sterile skin inflammation, the epidermis and macrophages uniquely depend on glycolysis and the TCA cycle, respectively. This compartmentalisation is initiated by ROS-induced HIF-1α stabilization leading to enhanced glycolysis in the epidermis. The end-product of glycolysis, lactate, is then exported by epithelial cells and utilized by the dermal macrophages to induce their M2-like fates through NF-κB pathway activation. In addition, we show that psoriatic skin disorder is also driven by such lactate metabolite-mediated crosstalk between the epidermis and macrophages. Notably, small-molecule inhibitors of lactate transport in this setting attenuate sterile inflammation and psoriasis disease burden, and suppress M2-like fate acquisition in dermal macrophages. Our study identifies an essential role for the metabolite lactate in regulating macrophage responses to inflammation, which may be effectively targeted to treat inflammatory skin disorders such as psoriasis. Synopsis: Inflammation alters skin tissue metabolism, however, the consequences for immune cell effector function remain unclear. Here, in vivo work in mice uncovers a ROS/HIF-1α-induced metabolic crosstalk between epidermal cells and macrophages during sterile inflammation, which aggravates disease progression. Induced skin inflammation shifts metabolic preferences to glycolysis and the TCA cycle in the epidermis and in macrophages, respectively. Inflammation-induced metabolic compartmentalisation is bridged by lactate secreted from the epidermis. Inhibition of lactate transport leads to reduced macrophage-mediated ECM degradation and in turn, inflammation. Inhibition of lactate transfer attenuates psoriasis symptoms in a imiquimod-induced mouse model. Lactate produced via glycolysis in epidermal cells activates NF-κB signaling and M2-like pro-remodeling phenotypes in dermal macrophages. [ABSTRACT FROM AUTHOR]

This article examines the effects of exercise on immune function, specifically inflammation and cardiovascular health. It discusses how exercise can stimulate the production of anti-inflammatory cytokines and leukocytes, aiding in tissue repair and reducing inflammation. However, intense exercise has been found to temporarily suppress the immune system and decrease the effectiveness of anti-inflammatory cytokines in individuals at risk for heart disease. The study also investigates the impact of exercise on monocyte polarization and finds that exercise does not significantly influence the polarization of monocytes towards pro-inflammatory or anti-inflammatory states. The study emphasizes the importance of measuring both anti-inflammatory activity and phenotype polarization when studying the effects of exercise on inflammation. Further research is needed to understand the effects of different exercise protocols on immune function, particularly in less active individuals, and to explore sex differences. Additionally, more research is warranted on the mechanisms by which exercise affects monocyte subset polarization and the production and effects of other inflammatory cytokines. Overall, this study provides valuable insights into the relationship between exercise and inflammation, laying the groundwork for future research in exercise immunology. [Extracted from the article]

Psoriasis is a chronic inflammatory skin disorder that affects a significant portion of the global population. It is characterized by the rapid proliferation of keratinocytes and a shortened turnover time. Psoriasis is also associated with metabolic syndrome and obesity. Previous research has shown that glucose uptake is important for keratinocyte proliferation, while the tricarboxylic acid (TCA) cycle is crucial for their differentiation. In psoriasis, there is an increase in GLUT1 expression, indicating enhanced glycolytic activity. Lactate, produced through glycolysis, contributes to ATP production through the TCA cycle. However, the specific mechanisms of lactate metabolism in psoriatic keratinocytes are still unclear. A recent study re-analyzed single-cell RNA sequencing data from psoriasis patients and found significant gene expression differences between healthy individuals and psoriasis patients. Psoriatic undifferentiated keratinocytes showed upregulation of glucose transporter genes and cell proliferation markers, while differentiated keratinocytes exhibited elevated expression of inflammatory markers. Pathway analysis revealed an increase in genes related to cell proliferation and aerobic respiration in psoriatic keratinocytes. Immunostaining confirmed the upregulation of GLUT1 and MCT1 in psoriatic undifferentiated keratinocytes, indicating enhanced glucose and lactate uptake. This metabolic shift promotes cell proliferation through glycolysis and supports differentiation through the TCA cycle, contributing to the pathology of psoriasis. Further research using in vitro and in vivo models is needed [Extracted from the article]

The incorporation of isolated Sn (IV) and Zr (IV) ions into silica frameworks is attracting widespread attention, which exhibits remarkable catalytic performance (conversion, selectivity, and stability) in a broad range of reactions, especially in the field of biomass catalytic conversion. As a representative example, the conversion route of carbohydrates into valuable platform and commodity chemicals such as lactic acid and alkyl lactates, has already been established. The zeotype materials also possess water‐tolerant ability and are capable to be served as promising heterogeneous catalysts for aqueous reactions. Therefore, dozens of Sn‐ and Zr‐containing silica materials with various channel systems have been prepared successfully in the past decades, containing 8 membered rings (MR) small pore CHA zeolite, 10‐MR medium pore zeolites (FER, MCM‐56, MEL, MFI, MWW), 12‐MR large pore zeolites (Beta, BEC, FAU, MOR, MSE, MTW), and 14‐MR extra‐large pore UTL zeolite. This review about Sn‐ and Zr‐containing metallosilicate materials focuses on their synthesis strategy, catalytic applications for diverse reactions, and the effect of zeolite characteristics on their catalytic performances. [ABSTRACT FROM AUTHOR]

The development of effective and stable non‐precious catalysts for hydrogenation of ester to diols remains a challenge. Herein, the catalytic hydrogenation of ethyl lactate (EL) to 1,2‐propanediol (1,2‐PDO) with supported Co catalysts derived from layered double hydroxides (LDHs) is investigated. Catalytic tests reveal that LDH‐derived Co catalysts exhibit the best catalytic performance with 98 % of EL conversion and >99 % of 1,2‐PDO selectivity at mild conditions, compared with other Co catalysts (supported on Al2O3, and TiO2) and LDH‐derived Cu catalysts. Due to the strong interaction among Co and Al matrix, the main composition is metallic Co0 and CoO after reduction at 600 °C. Besides, the catalyst shows good recyclability in the liquid phase hydrogenation. The superior catalytic performance can be attributed to the synergistic effect between Co0 and CoO, in which H2 molecule is activated on Co0 and EL is strongly adsorbed on CoO via hydroxyl groups. [ABSTRACT FROM AUTHOR]

Cardiac function is a major determinant of cardiopulmonary fitness. This study aimed to determine if novel echocardiographic myocardial function and efficiency parameters at rest can predict exercise performance during different types of prolonged high‐intensity endurance exercise. Echocardiography was performed before exercise in 40 healthy (75% males) 50.3 ± 9.1‐year‐old recreational athletes. Echocardiographic parameters at rest were compared with exercise performance assessed by power output during two different exercises: A lactate threshold and cardiopulmonary exercise test (La‐CPET) and a 91‐km mountain bike sport cycling race. The La‐CPET had a median duration of 43 (40, 45) minutes and a mean power output of 2.9 ± 0.5 W/kg. The race had a median duration of 236 (214, 268) minutes and a mean power output of 2.1 ± 0.5 W/kg. There was moderate left ventricular (LV) dilatation in individuals with the highest performance. The myocardial efficiency parameter, global wasted work (GWW), was positively correlated with race duration (rho = 0.42, p = 0.008) and negatively correlated with mean power output during both the La‐CPET (rho = −0.43, p = 0.007) and the race (rho = −0.44, p = 0.005). In multivariable models, including LV volumes, left GWW remained an independent predictor of race duration (beta = 0.40, p = 0.007) and of mean power output during the La‐CPET (beta = −0.40, p = 0.006) and the race (beta = −0.43, p = 0.003). The novel echocardiographic myocardial efficiency parameter, GWW, measured at rest, is an independent predictor of prolonged high‐intensity endurance exercise performance in healthy middle‐aged athletes. These findings suggest that resting myocardial efficiency parameters may aid the identification of exercise‐induced LV dilatation. Highlights: What is new? The novel echocardiographic parameter global wasted work represents a measure of myocardial efficiencyThis is the first study to demonstrate that global wasted work at rest is a marker of exercise‐induced cardiac remodeling and a predictor of exercise performance What are the clinical implications? Global wasted work at rest may be used to predict exercise performance levelGWW may aid in separating exercise‐induced from pathological left ventricular dilatation [ABSTRACT FROM AUTHOR]

Hypoxic exercise, which can induce arterial and tissue deoxygenation, promotes physiological adaptations. However, reduced oxygen availability can lower the absolute training intensity (i.e., mechanical stress). Adding normoxic recovery to sprint interval exercise (SIE) is one potential approach to strike a balance between providing a hypoxic stimulus and maintaining the absolute training intensity. However, the effects of adding normoxic recovery to SIE on performance and physiological responses are uncertain. We tested the hypothesis that hypoxic SIE with normoxic recovery enhances arterial deoxygenation and muscle deoxygenation levels without impeding performance compared to an entirely normoxic condition. On separate days, seven male sprinters performed 4 × 30‐s 'all‐out' cycle sprints with 4.5‐min recovery with hypoxic exposure (FiO2: 12.7%O2) applied continuously (hypoxia, HYP), intermittently during sprint periods only (intermittent, INT), or not at all (normoxia, NOR). Power output, oxygen saturation, muscle oxygenation, surface electromyography (EMG) activity, heart rate, blood lactate concentration, and ratings of perceived exertion were measured. The total work significantly decreased in HYP than NOR (p < 0.05) and INT (p < 0.01). The aTrterial oxygen saturation was lower during HYP than NOR (∼86% vs. ∼97%; p < 0.001), while lower values were also obtained for INT than NOR during sprint periods (∼85% vs. ∼97%; p < 0.001) but not during recovery periods (∼96% vs. ∼97%). The heart rate differed (p < 0.05) between conditions (NOR: ∼164 bpm; INT: ∼160 bpm; HYP: ∼156 bpm). No other variables demonstrated significant differences between conditions. Adding hypoxia during exercise while recovering in normoxia did not compromise exercise capacity during SIE, despite inducing larger arterial deoxygenation levels compared to normoxia. Highlights: Utilizing severe hypoxia during exercise and normoxia during recovery induces a substantial hypoxic stimulus while safeguarding mechanical performance in sprinters.This approach maintains neuromuscular, metabolic, and perceptual parameters without any detrimental effects, ensuring athletes can perform at their best.Alternating hypoxia and normoxia during active and passive phases shows potential for optimizing hypoxic training, striking an ideal balance between the hypoxic stimulus and training intensity and load. [ABSTRACT FROM AUTHOR]

Introduction: Delayed graft function (DGF) is a frequent complication following kidney transplant. This study aimed to assess the association between early post‐operative lactate variation and DGF. Methods: This was a single center, retrospective cohort study between February 2021 and December 2022 in Saint–Louis Hospital (APHP, France). Venous lactate levels were measured immediately (H0) and 4 h (H4) after kidney transplant. The primary outcome was the occurrence of DGF (need for renal replacement therapy between transplantation and day 7). Secondary outcome was the occurrence of complications (i.e., death, vascular thrombosis, hemorrhagic shock, urological complications (hematoma, urinoma), local or systemic infection) between transplant and day 7. Results: Two hundred 12 patients were included, and 38 (17.9%) developed DGF. Venous lactate variation between H0 and H4 was higher in patients who developed DGF (−30 (IQR −83, −6)% vs. −15 (IQR −62, −11)%, p =.037), but the variation of level was more often positive (corresponding to an increased lactate production over time between H0 and H4) in patients who developed DGF ((28(85%) vs. 94(62%), p =.011). In multivariate logistic regression, positive venous lactate level variation between H0 and H4 was strongly associated with a reduced risk of developing DGF (OR.30 [.09–.79], p =.024). We did not find any association between post‐operative hyperlactatemia and occurrence of complications between transplant and day 7. Discussion: DGF is a frequent complication following kidney transplantation. Its early prediction could help physicians optimize treatment and protect the kidney. Early venous lactate variation after kidney transplant could help to predict the occurrence of DGF. [ABSTRACT FROM AUTHOR]

The brain possesses intricate mechanisms for monitoring sodium (Na) levels in body fluids. During prolonged dehydration, the brain detects variations in body fluids and produces sensations of thirst and aversions to salty tastes. At the core of these processes Nax, the brain's Na sensor, exists. Specialized neural nuclei, namely the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), which lack the blood--brain barrier, play pivotal roles. Within the glia enveloping the neurons in these regions, Nax collaborates with Na+/K+-ATPase and glycolytic enzymes to drive glycolysis in response to elevated Na levels. Lactate released from these glia cells activates nearby inhibitory neurons. The SFO hosts distinct types of angiotensin II- sensitive neurons encoding thirst and salt appetite, respectively. During dehydration, Nax-activated inhibitory neurons suppress salt-appetite neuron's activity, whereas salt deficiency reduces thirst neuron's activity through cholecystokinin. Prolonged dehydration increases the Na sensitivity of Nax via increased endothelin expression in the SFO. So far, patients with essential hypernatremia have been reported to lose thirst and antidiuretic hormone release due to Naxtargeting autoantibodies. Inflammation in the SFO underlies the symptoms. Furthermore, Nax activation in the OVLT, driven by Na retention, stimulates the sympathetic nervous system via acid-sensing ion channels, contributing to a blood pressure elevation. [ABSTRACT FROM AUTHOR]