Search Results (195)

Cadmium (Cd) is a typical pollutant with strong toxicity even at low concentrations. In the marine environment, Cd is a problem of magnitude and ecological significance due to its high toxicity and accumulation in living organisms. The clam Meretrix meretrix is a useful bioindicator species for evaluating heavy-metal stress. This study investigated the extent of recovery from Cd²⁺-induced oxidative and immune impairments in M. meretrix gills achieved by short-term depuration. Clams were exposed to 3 mg/L Cd²⁺ for six days or three days followed by three days of depuration, and the Cd contents, morphological structure, osmoregulation, oxidative stress, and immune responses in the gills were evaluated. The results showed that gill Cd contents increased with exposure, reaching 9.857 ± 0.074 mg·kg⁻¹ on day 3 but decreased slightly to 8.294 ± 0.056 mg·kg⁻¹ after depuration, while reaching 18.665 ± 0.040 mg·kg⁻¹ on day 6 after continuous exposure. Histological lesions, including lamellar fusion, hemolymphatic sinus dilation, and ciliary degeneration, partially recovered after depuration. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels decreased significantly, while DNA-protein crosslinking rate (DPC) and protein carbonyl (PCO) showed minor reductions. Total antioxidant capacity (T-AOC) and the activities of Ca²⁺/Mg²⁺-ATPase (CMA), cytochrome c oxidase (COX), succinate dehydrogenase (SDH), and lactate dehydrogenase (LDH) increased by over 10% during depuration, though these changes were not statistically significant. Lysozyme (LZM) activity and MT transcript levels increased progressively with Cd exposure, indicating their suitability as biomarkers of Cd stress. Acid and alkaline phosphatase (ACP, AKP) activities and Hsp70 and Nrf2 mRNA transcripts exhibited inverted U-shaped response consistent with hormetic response. ACP and AKP activity levels rose by more than 20% after depuration, suggesting partial restoration of immune capacity. Overall, Cd exposure induced oxidative damage, metabolic disruption, and immune suppression in M. meretrix gills, yet short-term depuration allowed partial recovery. These findings enhance understanding of Cd toxicity and reversibility in marine bivalves and reinforce the usage of biochemical and molecular markers for monitoring Cd contamination and assessing depuration efficiency in aquaculture environments. Full article

Cytospora chrysosperma is a common opportunistically parasitic fungus that mainly infects forest trees, severely restricting the development of the fruit and forest industry. Surfactin is a secondary metabolite produced by Bacillus species and exhibits antifungal activity; Although the core antifungal mechanism of surfactin against plant pathogens has been extensively studied, our study found that surfactin can target the tricarboxylic acid cycle of C. chrysosperma. This study aimed to investigate the potential mechanism underlying the inhibitory effect of surfactin on C. chrysosperma. The results showed that surfactin had a significant inhibitory effect on C. chrysosperma, with a half-maximal effective concentration of 0.787 ± 0.045 mg/mL and a minimum inhibitory concentration of 2 mg/mL. Morphological observations revealed that surfactin significantly disrupted the morphology and ultrastructure of C. chrysosperma hyphae. FDA/PI staining indicated that surfactin affected the cell membrane integrity of C. chrysosperma, while DCFH-DA fluorescent staining and antioxidant enzyme activity assays demonstrated the accumulation of reactive oxygen species in hyphal cells following surfactin treatment. Additionally, the reduction in adenosine triphosphate content, as well as the decreased activities of ATPase and succinate dehydrogenase, suggested that energy production might be inhibited. Finally, MDC staining showed the occurrence of autophagosomes in C. chrysosperma hyphae after surfactin treatment, which may lead to hyphal death. Transcriptome analysis revealed that surfactin impaired the normal biosynthesis of the C. chrysosperma cell membrane and interfered with the tricarboxylic acid cycle by binding to citrate synthase, resulting in intracellular energy metabolism disorders. This study provides new insights into the potential mechanism by which surfactin inhibits hyphal growth of C. chrysosperma. Full article

This study addressed the optimal magnesium (Mg) requirement for juvenile largemouth bass (Micropterus salmoides) and assessed the effects of dietary Mg supplementation on growth performance, nutrient metabolism, and alleviation of heat stress in it. In this study, six diets with varying Mg levels (1.01, 1.26, 1.78, 2.24, 2.35, and 2.51 g/kg), designated as MG1, MG2, MG3, MG4, MG5, and MG6, respectively, were formulated using MgSO₄·7H₂O as the Mg source. These diets were fed to juvenile M. salmoides (initial body weight 2.27 ± 0.02 g) for 8 weeks. The growth performance of the MG4 group was significantly improved. In addition, Plasma GLU, LDL-C, and TG levels were significantly reduced in the MG4 group, while plasma HDL-C levels were increased. In terms of gene expression, glut2, g6pdh, ppar-γ, fas, elovl2, acc, and igf-1 were significantly upregulated in the MG4 and MG5 groups, while g6pase and ppar-α were significantly downregulated in the MG5 group. In the heat stress test, MG4 group exhibited enhanced antioxidant capacity, as evidenced by decreased plasma MDA levels and increased CAT activity, coupled with enhanced gill Na⁺/K⁺-ATPase activity. Gene expression results also showed that il-10 and bcl-2 were significantly upregulated in the MG4 group, while nf-κb, ifn-γ, il-8, tnf-α, casp3, casp8, bax, jnk2 and ask1 were significantly downregulated. Furthermore, the results of TUNEL immunofluorescence labeling analysis showed that the apoptotic index was significantly decreased in the MG2-MG6 groups. Overall, appropriate dietary Mg levels promoted growth performance, improved glucose metabolism, and induced lipid deposition in juvenile M. salmoides. Notably, Mg reduced oxidative damage by enhancing antioxidant enzyme activity, thereby modulating heat stress-induced Antioxidant–Inflammatory–Apoptotic of juvenile M. salmoides. Based on quadratic regression analysis of SGR and FCR, the optimal Mg requirement for juvenile M. salmoides was 2.04, and 2.15 g/kg, respectively. Full article

(1) Background: Repeated planting cycles and monoculture practices have led to widespread magnesium (Mg) deficiency in Chinese fir (Cunninghamia lanceolata) plantations. To gain clarity on how different Mg concentrations affect seedling growth and physiology, we designed the following experiment. (2) Methods: One-year-old seedlings were exposed to three Mg concentration treatments: High (HM), Medium (MM), and Low (LM). Their responses were evaluated in terms of growth traits, photosynthetic activity, and chloroplast structure. (3) Results: Both HM and LM significantly affected leaf development, with LM having the strongest impact. LM disrupted chloroplast structure, causing thylakoid membrane rupture, mitochondrial damage, accumulation of osmiophilic granules, and increased spacing between chloroplasts and cell walls. LM also impaired photosynthesis, lowering the net photosynthetic rate (Pn) and peroxidase (POD) activity, while increasing malondialdehyde (MDA) levels. Leaf growth was reduced, as shown by smaller leaf area and lower biomass. In contrast, HM temporarily enhanced some physiological traits, including intercellular CO₂ concentration (Ci), transpiration rate (Tr), leaf dry matter content (LDMC), and ATPase activity, though it also reduced Fv/Fo compared to MM. (4) Conclusions: Both high and low Mg concentration negatively affected photosynthesis, with Mg deficiency causing the most severe damage. These findings highlight the importance of managing soil Mg levels to maintain healthy growth and productivity in C. lanceolata plantations. Full article

Background: Resistance exercise (RE) is recognized for promoting the development of muscle strength and mass, as well as contributing positively to cardiovascular health. The combination of this type of exercise with the intake of foods rich in bioactive compounds, such as camu-camu (Myrciaria dubia), and creatine supplementation may be an interesting strategy to enhance the cardiovascular system. Objective: This study aimed to evaluate the effects of RE and supplementation with camu-camu and creatine on oxidative balance, mineral content, ATPase enzyme activity, and histological changes in the heart of Wistar rats. Methods: Forty-eight adult rats were divided into eight groups, with or without RE. The groups received a control diet (AIN-93M), camu-camu (200 mg/kg/day), creatine (300 mg/kg for 7 days and 50 mg/kg/day thereafter), or a combination of both. The RE protocol was performed on a vertical ladder three times a week for eight weeks. At the end, the animals were anesthetized and euthanized for tissue collection. Results: The trained control group that received a standard diet (AIN-T) showed greater activity of superoxide dismutase and catalase. The trained group receiving creatine and camu-camu supplementation (CC + Cr-T) showed higher total antioxidant capacity (FRAP), increased Mg²⁺-ATPase activity, higher nitric oxide levels, and a greater diameter of cardiac muscle fibers. No pathological changes were observed in heart histology in any group, indicating preservation of tissue integrity. Conclusions: RE associated with camu-camu and creatine supplementation may be an effective strategy for modulating antioxidant and functional aspects of the heart. Full article

Background: Multidrug resistance (MDR), primarily driven by P-glycoprotein (P-gp)-mediated drug efflux, presents a significant challenge in cancer therapy, contributing to chemotherapy failure and poor patient outcomes. Objectives: In this study, we explored the potential of manidipine (MA), a clinically approved calcium channel blocker, to reverse P-gp-mediated MDR through modulation of calcium signaling via nuclear factor of activated T cells 2 (NFAT2). Methods: Paclitaxel (PTX) resistance ABCB1-overexpressing cancer in vitro and in vivo were used for evualting the anti-MDR effects of MA, as well as the underlying mechanism with siRNA of NFAT2. Results: We found that MA at non-toxic concentrations (0.6–5.4 μM) significantly sensitize drug-resistant colorectal (HCT-8/T) and non-small cell lung (A549/T) cells to PTX, reducing its IC₅₀ by up to 1328-fold in vitro models. Mechanistically, MA inhibited P-gp efflux activity without altering its expression, as shown by an increased intracellular accumulation of doxorubicin and Flutax-2 (2.3- and 3.1-fold, respectively) and dose-dependent modulation of ATPase activity (EC₅₀ = 4.16 μM). Notably, MA reduced intracellular calcium levels (52% reduction, p < 0.001) and downregulated NFAT2, an oncogene overexpressed in resistant cells. In vivo, MA (3.5 mg/kg) synergizes with PTX to inhibit tumor growth by 68% (p < 0.001) in A549/T xenograft model, without an observable decrease in weight. Conclusions: In sum, all these results position MA as a novel NFAT2 inhibitor to overcome P-gp-mediated MDR via modulating calcium signaling, which points to further investigation for its clinical applications. Full article

Bacillus subtilis DinG/XPD-like paralogues, DinG and YpvA, have been implicated in overcoming replication stress. DinG possesses a DEDD exonuclease and DNA helicase domains, whereas YpvA lacks the DEDD exonuclease domain. We report that DinG·Mg²⁺ (hereafter referred to as DinG) degrades linear single-stranded (lss) DNA with 3′→5′ polarity and binds lssDNA with higher affinity than its exonuclease-deficient mutant DinG D10A E12A. DinG’s ssDNA-dependent ATPase activity neither stimulates nor inhibits DNA degradation. When bound to the 3′-end of forked DNA, DinG destabilises and degrades the substrate; however, in the presence of ATP, DinG dissociates before reaching the duplex junction. DinG degrades the RNA strand within RNA–DNA hybrids but does not cleave lssRNA unless complexed with Mn²⁺. DinG removes genomic R-loops, as RnhC and PcrA do. DinG physically interacts with RecA and PolA and functions in the same pathway as translesion synthesis (TLS) DNA polymerases (DNAPs) to respond to both spontaneous and methyl methanesulphonate (MMS)-induced mutagenesis. DinG-mGold forms spontaneous foci at or near replication forks, which become enriched following MMS or rifampicin treatment. We propose that DinG contributes to mitigating replication stress by degrading R-loop barriers and facilitating TLS, potentially via RecA-linked mechanisms. Full article

This study aimed to elucidate the physiological, biochemical, and transcriptional regulatory responses of potato plants to iron deficiency stress. Two potato varieties were selected for analysis: 05P (high tuber iron content) and CI5 (low tuber iron content). Tissue culture seedlings of both varieties were subjected to iron deficiency, and the effects on stem length, root length, fresh weight, soluble sugar and protein contents, as well as the activities of superoxide dismutase (SOD), peroxidase (POD), malondialdehyde (MDA), and leaf chlorophyll content (SPAD) values were evaluated. Additionally, the impact of iron deficiency on zinc (Zn), magnesium (Mg), calcium (Ca), manganese (Mn), and copper (Cu) concentrations in different tissues were analyzed. Transcriptomic sequencing and quantitative real-time PCR (qRT-PCR) were performed on various seedling tissues. The results showed that iron deficiency significantly inhibited seedling growth and development, resulting in reduced plant height and fresh weight, increased root length, decreased leaf SPAD content, and elevated soluble sugar and protein concentration. SOD, POD, and MDA activities were also significantly increased. Elemental analysis revealed that iron deficiency enhanced the uptake and accumulation of Zn, Mg, Ca, Mn, and Cu across different tissues. Transcriptomic analysis identified differentially expressed genes (DEGs) significantly enriched in pathways related to photosynthesis, carbon metabolism, and ribosome function in roots, stems, and leaves. Iron deficiency induced the upregulation of H⁺-ATPase genes in roots (PGSC0003DMG400004101, PGSC0003DMG400033034), acidifying the rhizosphere to increase active iron availability. Subsequently, this was followed by the upregulation of FRO genes (PGSC0003DMG400000184, PGSC0003DMG400010125, PGSC0003DMG401009494, PGSC0003DMG401018223), which reduce Fe³⁺ to Fe²⁺, and activation of IRT genes, facilitating Fe²⁺ transport to various tissues. Iron deficiency also reduced SPAD content in leaves, negatively impacting photosynthesis and overall plant growth. In response, the osmotic regulation and antioxidant defense systems were activated, enabling the plant to mitigate iron deficiency stress. Additionally, the absorption and accumulation of other metal ions were enhanced, likely as a compensatory mechanism for iron scarcity. At the transcriptional level, iron deficiency induced the expression of genes involved in metal absorption and transport, as well as those related to photosynthesis, carbon metabolism, and ribosomal function, thereby supporting iron homeostasis and maintaining metabolic balance under stress conditions. Full article

Background/Objectives: Recognizing the current limitations in rheumatoid arthritis (RA) treatments, especially in managing pain and inflammation, there is an urgent need to develop and explore new therapeutic strategies. In this study, we devised two innovative approaches using nanotechnology for treating RA. We evaluated the effectiveness of compound 4-(phenylselanyl)-2H-chromen-2-one (4-PSCO) in three forms: free, as well as in nanoemulsified (4-PSCO NE) and nanoencapsulated (4-PSCO NC) formulations. Methods: Arthritis was induced in mice by intraplantar injection of Freund’s complete adjuvant (CFA; 0.1 mL). The 4-PSCO free, 4-PSCO NE, and 4-PSCO NC (1 mg/kg, orally) treatments were administered daily for 15 days. We assessed disease signs, symptoms, mechanical and thermal sensitivities, neurobehavioral deficits, and activities of myeloperoxidase (MPO), Na⁺, K⁺-ATPase, and acetylcholinesterase (AChE), as well as oxidative stress markers. Results: Our study demonstrates, for the first time, that both 4-PSCO NC and 4-PSCO NE inhibit the clinical signs of RA in mice, including inflammation. Moreover, both formulations alleviated pain and anxiety behaviors while restoring AChE activity and decreasing oxidative stress in the cerebral cortex. Notably, only the 4-PSCO NC treatment increased the time animals spent in the open arms of the elevated plus-maze. It lowered TBARS levels in the cerebral cortex, spinal cord, and paws, showcasing its advantages over the free 4-PSCO and 4-PSCO NE. Conclusions: These findings highlight the therapeutic potential of 4-PSCO, especially the polymeric nanocapsule, as a practical option for treating both the symptoms and underlying mechanisms of RA. Full article

Background: Cardiac glycosides such as digoxin have been commonly used for patients with heart failure; however, their toxicity remains a main concern. 17βH-neriifolin (SNA209), a cardiac glycoside compound, has been recently isolated from Ceberra odollum Gaertn and was shown to improve the heart’s pumping ability in failing hearts ex vivo. Thus, this study aimed to investigate the potential use of SNA209 as a treatment for isoprenaline (ISO)-induced heart failure in rats. Methods: Forty male Wistar rats were randomly divided into five groups. Heart failure was induced by isoprenaline (ISO, 10 mg/kg/s.c) for 14 days daily, followed by SNA209 treatment (5 mg/kg; p.o) for another 14 days daily. Control rats were given saline as a vehicle for ISO and DMSO as a vehicle for SNA209. Results: Systolic and diastolic blood pressure (SBP and DBP) in all ISO-treated groups were significantly increased compared to the control group (p < 0.05), and SNA209 treatment managed to reduce the SBP and DBP. Additionally, SNA209 treatment significantly increased the heart rate and normalized the ECG parameters in ISO-treated rats. Pro-B-type natriuretic peptide and troponin T level, a cardiac injury markers, was remarkably reduced by SNA209 in the ISO-treated group. Cardiac hypertrophy was evident in increased cardiomyocyte size in ISO groups; however, SNA reduced the cardiomyocyte size. The left ventricular developed pressure (LVDP) in ISO treated with SNA209 was significantly raised, indicating a chronotropic effect. Cardiac Na⁺/K⁺-ATPase expression of the α1 subunit, sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase 2a (SERCA2a), and sodium–calcium exchanger subunit were significantly increased in the SNA treatment groups. Conclusions: The SNA 209 treatment improved cardiac function and structure, likely via modulating intracellular calcium management, so underscoring its potential as an adjuvant therapy for heart failure. Full article

Background: Empagliflozin, a sodium–glucose cotransporter 2 (SGLT2) inhibitor, improves outcomes in heart failure (HF) patients, yet inter-individual variability in response remains unclear. Genetic variants in Brain-Derived Neurotrophic Factor BDNF (rs6265) and ATPase Sarcoplasmic/Endoplasmic Reticulum Ca²⁺ Transporting 2 ATP2A2 (rs1860561) may influence the treatment efficacy. Objective: To assess the association of BDNF and ATP2A2 polymorphisms with the response to low-dose empagliflozin (10 mg) in Pakistani patients with heart failure and a reduced ejection fraction (HFrEF). Methods: In this prospective study, 120 HF patients with an ejection fraction of 25–45% who had been on stable standard heart failure therapy for at least 3 months were initiated on 10 mg of empagliflozin. The brain natriuretic peptide (BNP) and LVEF left ventricular ejection fraction (LVEF) were assessed at 6 and 12 months. Genotyping for rs6265 and rs1860561 was performed via Sanger sequencing. A response was defined as a ≥5% EF increase or ≥20% BNP reduction. Associations were analyzed using chi-square and logistic regression. Results: Among 99 genotyped patients, BDNF T allele carriers (CT/TT) had a significantly lower EF (p = 0.028) and BNP (p < 0.001) response. The CC genotype was associated with improved outcomes (BNP OR: 7.70; EF OR: 5.97). For ATP2A2, the GG genotype showed a strong association with EF improvement (OR: 5.97; p = 0.001), with no BNP association. Variant allele frequencies were higher among Punjabis and Kashmiris than Pathans. Conclusions: BDNF rs6265 and ATP2A2 rs1860561 polymorphisms appear to influence the individual response to empagliflozin in HFrEF patients. These findings underscore the potential of pharmacogenetic profiling to guide personalized therapy and optimize treatment outcomes in heart failure. Full article

Glyphosate (GLY) and microcystin-LR (MC-LR) frequently co-occur in natural water bodies. In this study, a subacute exposure test was conducted on zebrafish treated with 3.5 mg/L GLY and 35 μg/L MC-LR, individually and in combination, for 21 d to determine their effects on the gills of zebrafish and their potential mechanisms. The hematoxylin and eosin staining and scanning electron microscopy examination results showed that GLY and MC-LR exposure caused structural damage to gills. Biochemical analysis revealed Na⁺-K⁺-ATPase activity decreased, and the levels of reactive oxygen species, 8-hydroxy-2′-deoxyguanosine, and malondialdehyde increased, inducing oxidative damage to DNA and lipids of gills. Meanwhile, the inflammatory and immune function of the gill was significantly influenced, as evidenced by the alteration of the expression of tumor necrosis factor-α, interleukin-1β, complement 3, and immunoglobulin M. RNA-seq results revealed that GLY and/or MC-LR treatment induced transcriptional changes in the fish gills, which may affect various biological functions, and the lipid metabolism disruption potentially involved in the aforementioned process. Integrating histopathological, biochemical, and transcriptomic analyses, this study revealed that both individual and combined exposures to GLY and MC-LR had adverse effects on zebrafish gills, with combined exposure appears to result in more pronounced adverse effects, potentially compromising fish health. Full article

Salvia officinalis is an aromatic plant of Mediterranean origin traditionally used to treat inflammatory, cardiovascular, endocrine, and digestive diseases. In this work, the ability of the Salvia officinalis extract in the treatment of gastric ulcers was evaluated, and an innovative administration system was proposed to increase the therapeutic effect of this plant. Salvia officinalis ethanolic extract was prepared and analyzed by HPLC/UV-DAD and encapsulated in a matrix based on gelatin and pectin using an emulsion–coacervation process. The prepared microcapsules were analyzed by laser particle size, optical microscopy, in vitro dissolution kinetics, and ex vivo bioadhesion. In order to determine the action mechanism of Salvia officinalis extract, in the treatment of gastric ulcer, the in vivo anti-ulcerogenic activity in rats, using the ulcer model induced by ethanol; the in vivo anti-Helicobacter pylori activity; and in vitro inhibitory activity of H⁺/K⁺-ATPase were carried out. These three biological activities were evaluated for ethanolic extract and microcapsules to determine the effect of formulation on biological activities. Ethanolic extract of Salvia officinalis was mainly composed of polyphenols (chlorogenic acid 7.43%, rutin 21.74%, rosmarinic acid 5.88%, and quercitrin 14.39%). Microencapsulation of this extract allowed us to obtain microcapsules of 104.2 ± 7.5 µm in diameter, an encapsulation rate of 96.57 ± 3.05%, and adequate bioadhesion. The kinetics of in vitro dissolution of the extract increase significantly after its microencapsulation. Percentages of ulcer inhibition for 100 mg/kg of extract increase from 71.71 ± 2.43% to 89.67 ± 2.54% after microencapsulation. In vitro H⁺/K⁺-ATPase-inhibiting activity resulted in an IC50 of 86.08 ± 8.69 µM/h/mg protein for free extract and 57.43 ± 5.78 µM/h/mg protein for encapsulated extract. Anti-Helicobacter pylori activity showed a similar Minimum Inhibitory Concentration (MIC) of 50 µg/mL for the extract and microcapsules. Salvia officinalis ethanolic extract has a significant efficacy for the treatment of gastric ulcer; its mechanism of action is based on its gastroprotective effect, anti-Helicobacter pylori, and H⁺/K⁺-ATPase inhibitor. Moreover, the microencapsulation of this extract increases its gastroprotective and H⁺/K⁺-ATPase-inhibiting activities significantly. Full article

The deterioration of uterine calcium transport capacity induced by aging is a common problem for late-laying period hens, causing decline in eggshell quality. This study aimed to investigate the effects and possible regulatory mechanisms of dietary puerarin (PU) on calcium transport and eggshell quality in aged hens. Two hundred eighty-eight Hubbard Efficiency Plus broiler breeder hens (50-week-old) were randomly allocated to three dietary treatments containing 0, 40, or 200 mg/kg puerarin (PU), with 8 replicates of 12 birds each, for an 8-week trial. The results demonstrated that dietary PU ameliorated the eggshell thickness and strength, which in turn reduced the broken egg rate (p < 0.05). Histological analysis showed that PU improved uterus morphology and increased epithelium height in the uterus (p < 0.05). Antioxidative capacity was significantly improved via upregulation of Nrf2, HO-1, and GPX1 mRNA expression in the uterus (p < 0.05), along with enhanced total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-PX) activity, and decreased levels of the oxidative stress marker malondialdehyde (MDA) (p < 0.05). Meanwhile, PU treatment reduced the apoptotic index of the uterus, followed by a significant decrease in expression of pro-apoptotic genes Caspase3 and BAX and the rate of BAX/BCL-2. Additionally, calcium content in serum and uterus, as well as the activity of Ca²⁺-ATPase in the duodenum and uterus, were increased by dietary PU (p < 0.05). The genes involved in calcium transport including ERα, KCNA1, CABP-28K, and OPN in the uterus were upregulated by PU supplementation (p < 0.05). The 16S rRNA gene sequencing revealed that dietary PU supplementation could reverse the age-related decline in the relative abundance of Bacteroidota within the uterus (p < 0.05). Overall, dietary PU can improve eggshell quality and calcium transport through enhanced antioxidative defenses and mitigation of age-related uterine degeneration. Full article

Rising water temperatures due to climate change pose a significant threat to Phoxinus lagowskii, a cold-water fish that is ecologically vital to the high-latitude regions of China. This study assessed heat stress effects on behavioral, hematological, histological, physiological, and molecular responses in P. lagowskii. The critical maximum temperature (CT_max) was determined using the loss of equilibrium (LOE) method, with the CT_max reaching 29 °C. Elevated temperatures lead to an increase in the OBR. Fish were subjected to acute heat stress at 28 °C (below CT_max) for 48 h, with samples collected during the 48 h period. RBC, WBC, HGB, and HCT significantly increased during heat stress but decreased 12 h after heat stress. The levels of serum cortisol and blood glucose after heat stress were significantly higher than those in the control group. After heat stress, the height of the ILCM in the gills increased significantly, and the liver exhibited vacuolar degeneration and hypopigmentation. The activities of Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase in the gills initially increased and then decreased over the duration of heat stress. Most enzyme activities (PK, LDH, PFK, and HK) decreased during heat stress, while LPL and HL levels increased, indicating that lipid metabolism was the primary utilization process under heat stress. There was an increase in SOD activity at 12 h, followed by a decrease at 24 h, and an increase in CAT activity under heat stress. Integrated biomarker response (IBR) and principal component analysis (PCA) were employed to synthesize multi-level responses. The IBR values reached their peak at 3 h and 48 h of heat stress. We observed an upregulation of heat shock proteins (Hsp70, Hsp90, and Hsc70) as well as interleukin-10 (IL-10) in response to heat stress. Our findings offer novel insights into the mechanisms underlying the heat stress response in P. lagowskii, thereby enhancing our understanding of the effects of heat stress on cold-water fish. Full article