Search Results (502)

Saline–alkali stress severely restricts cucumber (Cucumis sativus L.) growth by disrupting ion balance, water status, photosynthesis, and redox homeostasis. Here, we examined the effects of exogenous selenium (Se) on cucumber seedlings exposed to NaHCO₃ stress. Se supplementation improved plant growth and root activity and partly restored photosynthetic performance by maintaining chlorophyll content, gas exchange, and chlorophyll fluorescence. Se reduced oxidative injury through lower ROS and MDA levels and by enhancing antioxidant enzyme activities together with the AsA–GSH cycle. In parallel, Se moderated ion toxicity by limiting Na⁺ accumulation, increasing K⁺, Ca²⁺, and Mg²⁺ uptake, and stimulating H⁺-ATPase and H⁺-PPase activities. Enhanced TCA cycle activity and organic acid accumulation suggested improved energy metabolism and ionic regulation. Se also promoted osmotic adjustment via soluble sugars and proline, and upregulated aquaporin genes (PIP1;2 and PIP2;4) to sustain water transport. Moreover, Se increased salicylic acid levels by upregulating CsPAL and CsICS, pointing to a role of SA signaling in Se-induced tolerance. Full article

Background/Objectives: Marine microorganism metabolites are structurally unique secondary metabolites possessing therapeutic potential. The current study aims to identify a novel ATPase regulator using a newly established bidirectional activity evaluation system to screen for microbial metabolites that inhibit the activities of Na⁺-K⁺-ATPase or Ca²⁺-Mg²⁺-ATPase. Methods: A total of 1258 marine microbial strains were isolated from sea mud in Zhoushan, Zhejiang. Results: The extract of strain ZSDH2536 exhibited Na⁺-K⁺ and Ca²⁺-Mg²⁺-ATPase inhibitory activity and was identified as Sirastachys pandanicola based on morphological and molecular phylogenetic analyses. The secondary metabolite was tentatively identified in the ZSDH2536 strain as a bisindole compound, and named Pandanicoline based on ¹H-NMR, ¹³C-NMR and high-resolution mass spectrometry analysis. The chemical formula of Pandanicoline is C₅₁H₆₈N₂O₁₀, with an isotopic mass of 868.4874 Da. The maximum inhibition rate of Pandanicoline on Na⁺-K⁺ and Ca²⁺-Mg²⁺-ATPase was 36.37% and 37.27%, respectively. Moreover, in silico analysis also showed the binding energy of Pandanicoline with Na⁺-K⁺-ATPase was −9.124 kcal/mol and with the Ca²⁺-Mg²⁺-ATPase complex was −10.47 kcal/mol. Conclusions: The strain ZSDH2536 represents a promising source of dual inhibitors targeting Na⁺-K⁺ and Ca²⁺-Mg²⁺-ATPase. Pandanicoline exhibits potential as a lead compound for regulating ion homeostasis, providing new opportunities for further investigation into its mechanism and therapeutic applications. Full article

Low temperature critically pressures insect pest distributions and population dynamics; however, integrated understanding of cold stress responses in invasive pests, particularly at the adult stage, remains limited. Here, we investigated the integrated physiological, biochemical, metabolomic and transcriptomic responses of Tuta absoluta (Meyrick, 1917) exposed to control (CT: 25 °C), moderate cold stress (MCS: 15 °C) and severe cold stress (SCS: 5 °C) conditions. Our results revealed that low-temperature stress impaired T. absoluta emergence, survival, fecundity and egg hatching in a stress intensity-dependent manner. Also, low temperature reduced the olfactory-mediated host-seeking behaviors of T. absoluta females. The biochemical analyses revealed depletion of triglycerides, glycogen and Na⁺/K⁺-ATPase activity alongside compensatory trehalose accumulations, while antioxidant enzyme activities (SOD, POD, CAT) were differentially modulated indicating progressive oxidative defense impairment under low temperature. Untargeted metabolomic profiling identified extensive differential metabolite accumulations, revealing systematic dysregulation of alkaloid biosynthesis, amino acid metabolism and central carbon metabolic pathways. Transcriptomic analysis identified several differentially expressed genes (DEGs) enriched in thermogenesis, oxidative phosphorylation, MAPK signaling and neurodegeneration-associated pathways. Furthermore, integrative transcriptome–metabolome analysis revealed coordinated gene–metabolite regulatory networks scaling systematically with cold stress intensity. These findings advance our mechanistic understanding of thermal stress adaptations in T. absoluta and may contribute to the development of climate-informed pest management strategies. Full article

Acute heart failure (AHF) and cardiogenic shock (CS) remain major causes of cardiovascular morbidity, mortality, and healthcare utilization worldwide. Although inotropic agents are central to the management of low-output states, their clinical utility is fundamentally constrained by mechanisms that increase myocardial oxygen consumption, disrupt calcium homeostasis, and promote arrhythmogenesis, without improving long-term outcomes. These limitations reflect not only pharmacological shortcomings, but a broader conceptual reliance on amplification of intracellular calcium flux as the primary means of augmenting contractility. While effective in increasing cardiac output, this strategy imposes substantial energetic and electrophysiological costs and fails to address key abnormalities of the failing myocardium, including impaired calcium recirculation and diastolic dysfunction. Istaroxime is a first-in-class agent that combines Na⁺/K⁺-ATPase inhibition with enhancement of sarcoplasmic reticulum Ca²⁺-ATPase (sarcoplasmic reticulum Ca²⁺-ATPase isoform 2a (SERCA2a)) function, thereby modulating both calcium availability and reuptake. This dual mechanism promotes a more coordinated pattern of excitation–contraction coupling, integrating systolic augmentation with improved diastolic relaxation. Early clinical studies demonstrate a distinct hemodynamic profile characterized by increased stroke volume, preservation of heart rate, and stabilization or elevation of arterial pressure. These properties suggest a potential role for istaroxime in specific hemodynamic phenotypes, particularly hypotensive AHF and early cardiogenic shock, where conventional inotropes are limited by tachycardia or vasodilatory effects. However, current evidence is limited to phase II studies focused on hemodynamic endpoints, and the impact of istaroxime on survival, organ function, and disease progression remains unknown. Istaroxime represents a mechanistically distinct approach to inotropic therapy, shifting the paradigm from calcium amplification toward partial restoration of calcium cycling. Its clinical relevance will depend on whether this strategy can translate into improved patient outcomes—an objective that has thus far eluded the entire class of inotropic agents. Full article

Cardiotonic steroids (CTS) can modulate central nervous system function through their interaction with the Na⁺,K⁺-ATPase, affecting dopaminergic transmission. While the CTS ouabain is known to induce mania-like behavior and oxidative damage, the effects of other CTS are less clear. This study examined the effects of 14-day intracerebroventricular administration of 1.5 μL 100 μM marinobufagenin (MBG) on locomotion, gait, monoamine metabolism, and oxidative stress markers (MDA, SOD, catalase, MAO-B) in C57BL/6 mice. Chronic MBG caused increased locomotor activity and time spent in the center of the open field. Unlike ouabain, chronic MBG did not impair motor function, evaluated via gait analysis. MBG elevated striatal MAO-B activity and reduced prefrontal MDA levels, with no changes in SOD or catalase, indicating that it did not cause oxidative stress. However, it did affect dopamine and serotonin metabolism. Monoamine tissue content evaluation on day 15 showed increased dopamine turnover in the striatum and brain stem, and a decrease in the thalamus. Norepinephrine levels increased in the striatum and hippocampus. Serotonin turnover increased in the prefrontal cortex. These results indicate that chronic MBG increases locomotion and reduces anxiety-like behavior through region-specific modulation of dopaminergic and serotonergic signaling distinct from that caused by ouabain. Full article

To evaluate the effects of swimming training on growth, swimming performance, and osmoregulatory-related indices in juvenile coho salmon, freshwater-reared fish were subjected to current of 1 body length per second (BL·s⁻¹) from December 2024 to April 2025. Fork length, body weight, condition factor, insulin-like growth factor-1 (IGF-1), and gill and intestinal Na⁺/K⁺-ATPase (NKA) protein abundance were measured monthly, and critical swimming speed (U_crit) was evaluated after one month of training. Trained fish showed greater fork length in March and higher body weight in March and April than controls. The condition factor was higher in trained fish in February and March, but declined during spring smolt development. Swimming capacity was enhanced by training, as indicated by significantly higher U_crit. Mean IGF-1 levels did not differ between groups, but IGF-1 correlated positively with body size only in trained fish. No significant training effect was detected for either gill or intestinal NKA protein abundance, although gill NKA increased significantly in April, likely reflecting seasonal smoltification. In addition, IGF-1 was significantly correlated with gill NKA in trained fish in March. Collectively, these results indicate that sustained swimming training improves growth and swimming performance and may enhance associations among measured physiological variables during smoltification in juvenile coho salmon. Full article

Total suspended solids (TSS) have been shown to damage the structural integrity of fish gills, impairing their function, including gas exchange. However, studies showing linkages between gill damage due to TSS and fish performance are limited. There is a large diversity of fish species inhabiting aquatic environments, and whether the TSS impact on gill function is similar across a range of species has yet to be explored. Here, we exposed multiple species, including salmonids (rainbow, brook and cutthroat trout) and cyprinids (fathead minnow and longnose dace) to a range of TSS concentrations (0–1000 mg L⁻¹) for 4 d and assessed damages to gill structure (filament thickness, lamellae thickness, oxygen diffusion distance, lamellae length, epithelial lifting, and interlamellar distance) using confocal microscopy. All species tested showed similar gill structural damage, including thicker lamellae, longer oxygen diffusion distances, and reduced respiratory surface area, at concentrations ≥ 100 mg L⁻¹ TSS. To assess whether gill damage corresponds to performance dysfunction, we tested the metabolic rate and swimming capacity of a salmonid (rainbow trout) and a cyprinid (fathead minnow) after exposure to 100 mg L⁻¹ TSS using swim tunnel respirometry. Trout showed lower routine metabolic rate (RMR) and maximum metabolic rate (MMR) after TSS exposure and were unable to reach the higher swimming speeds attained by unexposed fish. Fathead minnows showed no difference in the RMR after TSS exposure, but, like trout, had a lower MMR and were unable to attain the higher swimming speed of the control fish. Both species showed a ~35% reduction in the critical swimming speed (U_crit). These findings reveal that environmentally realistic TSS concentrations damage gill structure, impair fish swimming performance, and may compromise their ability to cope with energy-demanding activities, including additional biotic and abiotic stressors. Full article

This study evaluated the effects of crayfish shell meal (CSM) processed by drying, enzymatic hydrolysis, or fermentation on juvenile largemouth bass (Micropterus salmoides). A total of 320 fish (initial body weight, approximately 5.69 g) were distributed into 16 tanks, with 20 fish per tank and four replicates per treatment. Four isonitrogenous and isoenergetic diets were prepared: a fish meal-based control diet (FM) and three diets containing 4.5% dried CSM (DCSM), enzymatically hydrolyzed CSM (ECSM), or fermented CSM (FCSM), in which fish meal was reduced from 45.0% to 39.6%, and were fed for 8 weeks. Compared with the FM group, DCSM significantly reduced final body weight, weight gain rate, specific growth rate, and protein efficiency ratio, and increased feed conversion ratio (p < 0.05). ECSM generally showed intermediate responses, whereas FCSM did not differ significantly from FM in these growth and feed utilization indices (p > 0.05). DCSM also significantly increased serum aspartate aminotransferase and blood urea nitrogen levels and induced a pro-inflammatory intestinal response, as indicated by decreased il10 and increased il1b and tnfa expression (p < 0.05). Compared with DCSM, FCSM significantly improved these serum and inflammatory indices, increased intestinal trypsin, Na⁺/K⁺-ATPase and γ-glutamyl transferase activities (p < 0.05), and showed more favorable antioxidant and gut microbiota responses. Overall, fermentation was more effective than enzymatic hydrolysis in improving the feeding value of CSM for largemouth bass. These results suggest that FCSM is a promising alternative ingredient for aquafeeds and may contribute to the high-value utilization of crayfish processing by-products. Full article

Nitrite is a key environmental challenge in intensive shrimp aquaculture, adversely affecting physiological regulation and survival. Although tolerant Penaeus vannamei families have been established by selective breeding, the basis of family-level variation in tolerance has yet to be clarified. In this study, nitrite-tolerant and nitrite-sensitive families were compared using survival analysis, transcriptomics, targeted qPCR validation, physiological assays, and RNA interference of representative transport-related genes. Under nitrite exposure, the tolerant family exhibited significantly higher survival and a distinct gill transcriptional response, characterized by stronger induction of acid–base and ion-transport genes, including carbonic anhydrase 2 (CA2), the Na⁺/K⁺-ATPase subunits ATP1A and ATP1B, as well as several V-type H⁺-ATPase-related genes. These transcriptional changes were accompanied by elevated ATP content and Na⁺/K⁺-ATPase activity, improved hemolymph pH stability, and reduced nitrite accumulation in both gill and hemolymph. RNAi-mediated knockdown of CA2 or ATP1B attenuated the nitrite-induced transport response, decreased ATP content and NKA activity, exacerbated hemolymph acidification, promoted internal nitrite accumulation, and ultimately reduced shrimp survival under nitrite stress. Family-based validation further showed that the tolerant family displayed higher survival than the sensitive family in the dsEGFP group, whereas this advantage was markedly reduced after CA2 or ATP1B knockdown under nitrite stress. These findings highlight that strengthened branchial ion transport and acid–base regulation represent key physiological mechanisms underlying nitrite tolerance in resistant shrimp families. Full article

Although the effectiveness of plant-derived essential oils (EOs) against several insect pests is well-documented, their high volatility presents a challenge. In this study, the potential to enhance the insecticidal activity of Satureja hortensis L. EO, an accessible natural agent, through nanoemulsification was assessed against the cosmopolitan pest Spodoptera frugiperda (J. E. Smith, 1797). The nanoemulsion of the EO (NEEO) was prepared using Tween 80 as the emulsifying agent and high-intensity ultrasonication. Oral bioassays indicated that the NEEO was more toxic (LC₅₀ = 0.922%) than the pure EO (LC₅₀ = 1.186%). Sublethal exposure to LC₃₀ of the NEEO caused evident reductions in preadult survival, developmental time, fecundity, and oviposition period, as well as the population growth parameter net reproductive rate (R₀). The exposure to the NEEO increased catalase (CAT), glutathione S-transferase (GST), and superoxide dismutase (SOD) actions and inhibited α-esterase (α-NE), β-esterase (β-NE), and cytochrome P450 (CYP450) actions. Both the NEEO and EO inhibited acetylcholinesterase (AChE) and Na⁺/K⁺-ATPase, with higher inhibition in the NEEO group. Generally, S. hortensis NEEO enhanced toxicity, intensified physiological perturbations, and caused greater negative impacts on population growth parameters. Consequently, nanoemulsification of S. hortensis EO can be considered an effective method to strengthen the insecticidal potential of this natural agent. Full article

Tumour necrosis factor-alpha (TNF-α) disrupts bioenergetic homeostasis in skeletal muscle cells through the suppression of ion-dependent ATPase activities, mitochondrial depolarisation, and impairment of antioxidant defences. Carvacrol, a phenolic monoterpenoid constituent of thyme and oregano essential oil, has been shown to exert cytoprotective effects in TNF-α-challenged L6 rat myoblasts. The mechanistic basis of these effects, specifically the relationship between membrane-associated ATPase function, mitochondrial polarisation status, and transcriptional regulation of metabolic stress-response genes, has not been formally characterised. L6 rat myoblasts were exposed to TNF-α (10 ng/mL, 1 h), then treated with carvacrol (6.25 µg/mL, 24 h) in a post-inflammatory rescue paradigm. Cell viability (MTT), membrane integrity (LDH), ion-dependent ATPase activities (Na⁺/K⁺, Ca²⁺, Mg²⁺), antioxidant enzyme activities (catalase, SOD), mitochondrial membrane potential (Muse™ MitoPotential flow cytometry), and SIRT1/AMPK mRNA expression were quantified. TNF-α significantly suppressed Na⁺/K⁺, Ca²⁺, and Mg²⁺-dependent ATPase activities (all p < 0.001), consistent with impaired membrane-associated bioenergetic function. Post-TNF-α carvacrol treatment partially restored all three ATPase activities (p < 0.05) and reduced the proportion of mitochondrially depolarised cells from 31.65 ± 4.25% to 19.0 ± 2.6% (p < 0.05). LDH release, catalase activity, and SOD activity were also significantly modulated. At the transcriptional level, carvacrol increased SIRT1 mRNA by 1.6-fold and AMPK mRNA by 2.0-fold relative to TNF-α-treated cells. An integrative bioenergetic model is proposed in which carvacrol’s membrane-intercalating properties restore the phospholipid environment required for ATPase conformational cycling, attenuating the Ca²⁺ overload that drives mitochondrial permeability transition, and thereby partially preserving Δψm. Transcriptional upregulation of SIRT1 and AMPKα may represent an adaptive response to residual energetic stress. The mechanistic relationships among these endpoints and the causal contribution of SIRT1 and AMPK to observed bioenergetic changes require protein-level and pathway-specific experimental validation. Full article

Saline-alkaline water is increasingly used for aquaculture. Qihe crucian carp (Carassius carassius) is one of the major economic aquacultural species in China; however, the impact of saline-alkaline water on this fish remains unclear. In this study, a 60 d chronic alkalinity stress experiment was conducted to investigate the effects on the growth, physiology, and muscle quality of Qihe crucian carp. One hundred and eighty juvenile fish (31.03 ± 0.71 g) were divided into three treatments (three replicate tanks per treatment, 20 fish per tank): a control group (freshwater), a CA20 group (20 mmol/L), and a CA40 group (40 mmol/L). Despite no effect on survival, alkalinity stress significantly impaired growth performance in both the CA20 and CA40 groups, leading to reductions in final body weight, weight gain rate, and specific growth rate. Similarly, the feed efficiency decreased with increasing alkalinity. Compared to the control group, the alkalinity groups exhibited elevated serum Na⁺ levels and higher gill Na⁺/K⁺-ATPase activity, but reduced Ca²⁺/Mg²⁺-ATPase activity. For histology, chronic alkalinity stress induced several changes in the gills, including wider filaments, shortened lamellae, and the increase in interlamellar distance. Regarding muscle nutritional composition, the contents of crude protein and amino acids and the proportions of polyunsaturated fatty acids showed a downward trend with rising alkalinity. Additionally, alkalinity stress significantly decreased muscle fiber density and hardness. Taking into account both growth performance and muscle quality, the suggested aquacultural alkalinity should be controlled below 20 mmol/L for Qihe crucian carp. In conclusion, these findings supported Qihe crucian carp as a promising candidate species for saline-alkaline water aquaculture, providing a scientific basis for the utilization of this special water resource. Full article

Metabolic syndrome (MeS) is a multifactorial disorder characterized by insulin resistance, dyslipidemia, hypertension, and obesity, and oxidative stress plays a key role in tissue damage in this syndrome. This study aimed to investigate this role in Na⁺/K⁺-ATPase (NKA) expression in skeletal muscle and to evaluate the effects of quercetin. A high-sucrose-diet-induced MeS model was established in Wistar albino rats (n = 32), and skeletal muscle tissues were analyzed. Biochemical parameters were measured, including aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total antioxidant status (TAS), total oxidant status (TOS), superoxide dismutase (SOD), and malondialdehyde (MDA). In addition, thioredoxin-1 (TRX1) and NKA protein expression levels were evaluated using Western blot analysis. In the MeS group, AST, TAS, TRX1, and NKA expression significantly decreased, while LDH, TOS, SOD, and MDA levels increased, indicating disrupted redox balance, elevated oxidative stress, and impaired antioxidant defense. Increased MDA and TOS levels reflected enhanced lipid peroxidation, whereas decreased TAS and TRX1 suggested reduced antioxidant capacity. Elevated SOD activity may indicate a compensatory response to excessive reactive oxygen species (ROS). The reduction in NKA expression may contribute to impaired ion transport and potential skeletal muscle dysfunction. Quercetin administration improved oxidative stress markers and partially restored NKA expression. These findings suggest that oxidative stress contributes to NKA dysfunction in MeS, and quercetin may have therapeutic potential by modulating oxidative stress and preserving enzyme function. Full article

Pomegranate peel is a food industry waste rich in polyphenols. To date, its effect in alleviating fatigue remains unclear. This study aimed to characterize the chemical composition of pomegranate peel polyphenols (PPPs), evaluate its antioxidant and anti-fatigue capacities, and investigate the underlying mechanism. In the current study, twenty main compounds, primarily flavonoids, phenolic acids, and anthocyanins, were identified from PPPs using LC-MS/MS. In H₂O₂-induced HepG2 cells, PPPs promoted cellular repair and reduced the production of intracellular malondialdehyde (MDA) and reactive oxygen species (ROS) via enhancing the activity of antioxidant enzymes (SOD, CAT, and GSH-Px). In the endurance swimming-induced fatigue mice model, PPPs prolonged mice exhaustion times, reduced accumulation of fatigue-related metabolites (BUN, LA, BA, LDH and CK), and alleviated liver and muscle tissue damage. Mechanistically, PPPs mitigated oxidative stress via activation of the Keap1/Nrf2 pathway, leading to increased expression of hemeoxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Furthermore, PPPs stimulated energy metabolism by activating the AMPK/PGC-1α/PPAR-α pathway, promoting mitochondrial biogenesis, enhancing glycogen storage, increasing ATPase activity (Na⁺-K⁺-ATPase, Ca²⁺-Mg²⁺-ATPase, and T-ATPase) and accelerating lipid β-oxidation. These findings suggest that PPPs is a promising anti-fatigue supplement and could be further utilized in the nutritional industry. Full article

Metabolic dysfunction, a hallmark of diet-induced obesity (DIO), is increasingly attributed to alterations in intestinal nutrient and electrolyte transport. Yet the mechanisms that drive obesity-associated functional alterations of intestinal transporters remain incompletely understood. In this context, the effects of a high-fat diet (HFD) induced obesity on sodium-dependent glucose co-transporter 1 (SGLT1), Na⁺/H⁺ exchanger 3 (NHE3), and Cl⁻/HCO₃⁻ exchangers (DRA/PAT1), the primary glucose, sodium, and chloride absorptive pathways in mice small intestinal villus cells, were investigated. SGLT1 activity significantly increased in intact villus cells and brush border membrane vesicles (BBMV) from HFD-fed mice. Kinetic analysis demonstrated reduced Km without a change in Vmax, indicating enhanced transporter affinity. Notably, SGLT1 mRNA and protein expression, including BBM localization, were unchanged. Basolateral Na⁺/K⁺-ATPase activity was decreased, excluding enhanced Na⁺ gradient generation as the mechanism for SGLT1 stimulation. In contrast, DRA/PAT1 activity was significantly increased in HFD-fed mice, and kinetic studies revealed elevated Vmax without a change in Km, indicating increased transport capacity. DRA/PAT1 mRNA, total protein, and BBM expression were all significantly elevated. NHE3 activity and expression remained unchanged. These findings demonstrate that DIO enhances intestinal glucose absorption by increasing SGLT1 affinity and chloride absorption by upregulating DRA/PAT1 transcription. These transporter-specific alterations may amplify nutrient absorption and contribute to metabolic dysregulation in obesity. Full article