Stress Response Research Articles

Synergistic effects of thermal stress and 4-nonylphenol on oxidative stress and immune responses in juvenile tilapia (Oreochromis niloticus).

Aquatic ecosystems face multiple stressors, including thermal fluctuations and chemical pollutants, which can detrimentally impact fish health and ecosystem integrity. This study investigates the individual and combined toxic effects of 4-nonylphenol (4-NP) and thermal stress on juvenile tilapia fish (Oreochromis niloticus). Four groups of fish were exposed to different stressors for 15days: control, thermal stress (35°C ± 1°C), 4-NP exposure (1mg/L), and a combination of thermal stress and 4-NP. Results reveal significant alterations in antioxidant enzyme activity, lipid peroxidation levels, and cytokine expression in response to stressors. Thermal stress and 4-NP exposure disrupt antioxidant defense mechanisms and increase oxidative stress. Thermal stress profoundly affects fish health and metabolism, impacting physiological functions and immunity. Thermal stress induces reactive oxygen species production, triggering antioxidant responses and affecting immune parameters. Exposure to 4-NP exacerbates oxidative stress, further compromising fish health. The observed increase in pro-inflammatory cytokines implies an immunostimulatory reaction to stressors. These findings underscore the complex interactions between environmental stressors, immune responses, and fish health. Further research is needed to fully understand these interactions and their implications for aquatic ecosystems. Implementing these biomarkers in ecological risk assessments can provide insights into the impacts of environmental stressors and inform conservation and management strategies in aquaculture.

Dynamic stress response and fatigue characteristics of tight sandstone reservoirs with pulsating hydraulic fracturing

Dynamic stress response and fatigue characteristics of tight sandstone reservoirs with pulsating hydraulic fracturing

EXTH-37. ALLOSTERIC MITOCHONDRIAL CLPP AGONIST ONC206 ALTERS STRESS RESPONSE, METABOLIC AND EPIGENETIC PROFILES TO ELICIT ANTI-CANCER EFFICACY IN HIGH-GRADE GLIOMAS

Abstract Dordaviprone (ONC201) is a dopamine receptor D2/3 (DRD2/3) antagonist and allosteric ClpP agonist that has demonstrated durable responses in recurrent H3 K27M-mutant glioma patients. ONC206, a derivative of ONC201 with nanomolar potency that also targets DRD2/3 and ClpP, is in Phase I trials for central nervous system tumors. We characterized target relevance, human ClpP binding, in vitro efficacy, downstream signaling and response determinants associated with ONC206 in high-grade gliomas (HGG). Co-crystallization with ClpP that assembles as a tetradecameric complex revealed an allosteric ligand interaction with distinctions in the ONC206-ClpP overall conformation relative to the ONC201-bound or apo complex, including an increase in the resolved pore size and decreased complex height. ONC206 was more potent than ONC201 in cell-free human ClpP casein/peptide degradation assays). Accordingly, HGG cell lines and patient-derived cells exhibited increased sensitivity to ONC206 relative to ONC201 and generally required a shorter duration of exposure. Unlike DRD2, CRISPR-mediated ClpP knockout in HGG cell lines blunted ONC206 sensitivity. Metabolomics revealed elevated α-ketoglutaric acid, α-hydroxyglutaric acid, and glutaric acid. Proteomics indicated inhibition of multiple mitochondrial pathways including OXPHOS and TCA cycle. TCA cycle enzyme α-ketoglutarate dehydrogenase (KGDH) was inhibited in a ClpP-dependent manner. Western blotting showed downregulated ClpX, and upregulated ATF4/CHOP, H3 K27me3 and H3 K36me3. Next-generation sequencing of acquired resistance cell lines, which exhibited cross-resistance to ONC201 and ONC206, revealed diverse ClpP missense mutations distributed across various monomer interfaces. Both intrinsic and well as ONC206-stimulated ClpP proteolysis were mitigated by these mutations, which was congruent with an absence of the tetradecameric assembly. These ClpP mutations recapitulated resistance and, conversely, wildtype ClpP overexpression restored sensitivity. Thus, allosteric ClpP agonism is a key determinant of ONC206 activity in HGG by altering stress response, metabolic, and epigenetic profiles.

Electrochemically Coupled Anaerobic Membrane Bioreactor Facilitates Remediation of Microplastic-Containing Wastewater

Ubiquitous microplastics (MPs) severely affect the efficiency of anaerobic membrane bioreactors (AMBR) for wastewater treatment and energy recovery by inhibiting the metabolic activity of anaerobic microorganisms. The electrochemical system can not only accelerate waste metabolism but also improve microbial resistance by promoting interspecies electron transfer within the system, which has broad application potential in the remediation of MPs wastewater. This paper attempts to evaluate the effect of electrical stimulation on the efficiency of biological wastewater treatment processes containing MPs employing an electrochemical system coupled to an anaerobic membrane bioreactor (ECAMBR). The results showed that although MP exposure inhibited methanogenic performance, electrical stimulation effectively alleviated this inhibitory effect. Further analysis showed that microplastics increased cell damage and affected enzyme activity, but electrical stimulation could affect the stress response of microorganisms, leading to changes in their cell viability and enzyme activities. The 16S-rRNA sequencing indicated that the highest abundance of hydrolytic–acidogenic bacteria Firmicutes and Bacteroidota was found at the phylum level, whereas at the genus level, it was Christensenellaceae_R-7_group, and methanogens were dominated by Methylomonas, Methyloversatilis, and Methylobacter. Functional prediction analysis indicated that carbohydrate metabolism, amino acid metabolism, and energy metabolism were the dominant metabolic pathways and that electrical stimulation could enhance their activities. This study demonstrated the important role of electrochemical stimulation in the remediation of wastewater containing high concentrations of MPs.

P14ARF forms meso-scale assemblies upon phase separation with NPM1.

NPM1 is an abundant nucleolar chaperone that, in addition to facilitating ribosome biogenesis, contributes to nucleolar stress responses and tumor suppression through its regulation of the p14 Alternative Reading Frame tumor suppressor protein (p14ARF). Oncogenic stress induces p14ARF to inhibit MDM2, stabilize p53 and arrest the cell cycle. Under non-stress conditions, NPM1 stabilizes p14ARF in nucleoli, preventing its degradation and blocking p53 activation. However, the mechanisms underlying the regulation of p14ARF by NPM1 are unclear because the structural features of the p14ARF-NPM1 complex were elusive. Here we show that p14ARF assembles into a gel-like meso-scale network upon phase separation with NPM1. This assembly is mediated by intermolecular contacts formed by hydrophobic residues in an α-helix and β-strands within a partially folded N-terminal portion of p14ARF. These hydrophobic interactions promote phase separation with NPM1, enhance p14ARF nucleolar partitioning, restrict NPM1 diffusion within condensates and nucleoli, and reduce cellular proliferation. Our structural analysis provides insights into the multifaceted chaperone function of NPM1 in nucleoli by mechanistically linking the nucleolar localization of p14ARF to its partial folding and meso-scale assembly upon phase separation with NPM1.

CSIG-21. THE ROLE OF GUT MICROBIOTA IN GLIOBLASTOMA: INSIGHTS FROM MICROBIOME-GENE EXPRESSION INTERACTIONS

Abstract Glioblastoma, the most aggressive form of primary brain tumor, remains a formidable clinical challenge due to its invasiveness and resistance to therapy. Emerging evidence suggests that the gut microbiome plays a crucial role in modulating cancer progression through complex interactions with host physiology. In this study, we investigated the influence of gut microbiota and tumor gene expression by analyzing stool and tissue samples from glioblastoma patients. Utilizing 16S rRNA sequencing of stool samples and NanoString gene expression analysis of tumor tissue samples, we explored the relationship between gut microbiome taxa and gene expression levels in tissue. Pathway analysis using KEGG and Gene Ontology databases was employed to elucidate the functional implications of these interactions. Our findings reveal contrasting effects of specific gut microbiota taxa and gene expression, with Fusobacterium demonstrating a potential oncogenic role, while Bifidobacteriaceae and Akkermansiaceae display potential tumor-suppressive effects. Fusobacterium is associated with the upregulation of key oncogenes and pathways promoting cancer cell survival, growth, and metabolism, whereas Bifidobacteriaceae and Akkermansiaceae are linked to the downregulation of genes involved in pathways promoting cancer cell survival and proliferation, such as MAPK signaling and stress response pathways, potentially inhibiting cancer cell growth. These results highlight the intricate interplay between gut microbiota composition and cancer biology and underscore the potential of gut microbiota modulation as a therapeutic strategy in glioblastoma management.

Disrupted Nitric Oxide Homeostasis Impacts Fertility through Multiple Processes Including Protein Quality Control.

Plant fertility is fundamental to plant survival and requires the coordinated interaction of developmental pathways and signaling molecules. Nitric oxide (NO) is a small, gaseous signaling molecule that plays crucial roles in plant fertility as well as other developmental processes and stress responses. NO influences biological processes through S-nitrosation, the posttranslational modification of protein cysteines to S-nitrosocysteine (R-SNO). NO homeostasis is controlled by S-nitrosoglutathione reductase (GSNOR), which reduces S-nitrosoglutathione (GSNO), the major form of NO in cells. GSNOR mutants (hot5-2/gsnor1) have defects in female gametophyte development along with elevated levels of reactive nitrogen species and R-SNOs. To better understand the fertility defects in hot5-2, we investigated the in vivo nitrosoproteome of Arabidopsis (Arabidopsis thaliana) floral tissues coupled with quantitative proteomics of pistils. To identify protein-SNOs, we used an organomercury-based method that involves direct reaction with S-nitrosocysteine, enabling specific identification of S-nitrosocysteine-containing peptides and S-nitrosated proteins. We identified 1102 endogenously S-nitrosated proteins in floral tissues, of which 1049 were unique to hot5-2. Among the identified proteins, 728 were novel S-nitrosation targets. Notably, specific UDP-glycosyltransferases and argonaute proteins are S-nitrosated in floral tissues and differentially regulated in pistils. We also discovered S-nitrosation of subunits of the 26S proteasome together with increased abundance of proteasomal components and enhanced trypsin-like proteasomal activity in hot5-2 pistils. Our data establish a method for nitrosoprotein detection in plants, expand knowledge of the plant S-nitrosoproteome, and suggest that nitro-oxidative modification and NO homeostasis are critical to protein quality control in reproductive tissues.

Decoding the Impact of a Bacterial Strain of Micrococcus luteus on Arabidopsis Growth and Stress Tolerance

Microbes produce various bioactive metabolites that can influence plant growth and stress tolerance. In this study, a plant growth-promoting rhizobacterium (PGPR), strain S14, was identified as Micrococcus luteus (designated as MlS14) using de novo whole-genome assembly. The MlS14 genome revealed major gene clusters for the synthesis of indole-3-acetic acid (IAA), terpenoids, and carotenoids. MlS14 produced significant amounts of IAA, and its volatile organic compounds (VOCs), specifically terpenoids, exhibited antifungal activity, suppressing the growth of pathogenic fungi. The presence of yellow pigment in the bacterial colony indicated carotenoid production. Treatment with MlS14 activated the expression of β-glucuronidase (GUS) driven by a promoter containing auxin-responsive elements. The application of MlS14 reshaped the root architecture of Arabidopsis seedlings, causing shorter primary roots, increased lateral root growth, and longer, denser root hairs; these characteristics are typically controlled by elevated exogenous IAA levels. MlS14 positively regulated seedling growth by enhancing photosynthesis, activating antioxidant enzymes, and promoting the production of secondary metabolites with reactive oxygen species (ROS) scavenging activity. Pretreatment with MlS14 reduced H2O2 and malondialdehyde (MDA) levels in seedlings under drought and heat stress, resulting in greater fresh weight during the post-stress period. Additionally, exposure to MlS14 stabilized chlorophyll content and growth rate in seedlings under salt stress. MlS14 transcriptionally upregulated genes involved in antioxidant defense and photosynthesis. Furthermore, genes linked to various hormone signaling pathways, such as abscisic acid (ABA), auxin, jasmonic acid (JA), and salicylic acid (SA), displayed increased expression levels, with those involved in ABA synthesis, using carotenoids as precursors, being the most highly induced. Furthermore, MlS14 treatment increased the expression of several transcription factors associated with stress responses, with DREB2A showing the highest level of induction. In conclusion, MlS14 played significant roles in promoting plant growth and stress tolerance. Metabolites such as IAA and carotenoids may function as positive regulators of plant metabolism and hormone signaling pathways essential for growth and adaptation to abiotic stress.

Female Wistar Kyoto More Immobile rats with genetic stress hyper-reactivity show enhanced contextual fear memory without deficit in extinction of fear.

The prevalence of post-traumatic stress disorder (PTSD) is higher in females than males, but pre-clinical models are established almost exclusively in males. This study is aimed to investigate the stress-enhanced fear learning model of PTSD in females. The model mirrors PTSD symptomology in males, whereby prior stress leads to extinction resistant exaggerated contextual fear memory. As stress reactivity is highly relevant to the study and risk for PTSD, females of the stress hyper-reactive Wistar Kyoto More Immobile (WMI) and its nearly isogenic control the Wistar Kyoto Less Immobile (WLI) strains were employed. Prior studies have shown WMI females presenting unchanged or enhanced fear memory in the stress-enhanced fear learning paradigm compared WLIs. The present study confirmed the enhanced fear memory following contextual fear conditioning in WMIs compared to WLI females, but this increased fear memory was neither exaggerated by prior stress nor showed extinction deficit. The novel stressor of a glucose challenge test resulted in subtle strain- and prior stress-induced differences in plasma glucose responses. However, fasting plasma corticosterone levels were lower, and rose slower in response to glucose challenge in WMI females, suggesting a PTSD-like dysfunctional stress response. Hippocampal expressions of genes relevant to both learning and memory and the stress response were decreased in stressed WMIs compared to WLI females, further suggesting a marked dysregulation in stress-related functions like in PTSD. Thus, although WMI females do not show extinction-resistant enhanced fear memory, they do present other characteristics that are relevant to PTSD in women.

Studying the Combined Impact of Salinity and Drought Stress-Simulated Conditions on Physio-Biochemical Characteristics of Lettuce Plant

Water scarcity and increasing salinity stress are significant challenges in the farming sector as they often exacerbate each other, as limited water availability can concentrate salts in the soil, further hindering plant growth. Lettuce, a crucial leafy vegetable with high nutritional value, is susceptible to water availability and quality. This study investigates the growth and development of lettuce plants under water scarcity and varying levels of salinity stress to identify effective strategies for reducing water consumption while maintaining or improving plant productivity. Field experiments were designed to simulate three drought levels (50, 75, and 100% of class A pan evaporation) and three salinity stress levels (control, 1500, and 3000 ppm NaCl), assessing their impact on lettuce’s morphological and biochemical parameters. The combination of reduced water supply and high salinity significantly hindered growth, underscoring the detrimental effects of simultaneous water deficit and salinity stress on plant development. Non-stressed treatment enhanced nitrogen, phosphorus, and potassium contents and progressively decreased with the reduction in water supply from 100% to 50%. Interestingly, higher salinity levels increased total phenolic, flavonoid, and antioxidant activity, suggesting an adaptive stress response. Moreover, antioxidant activity, evaluated through DPPH and ABTS assays, peaked in plants irrigated with 75% ETo, whether under control or 1500 ppm salinity conditions. The Yield Stability Index was highest at 75% ETo (0.95), indicating robust stability under stress. The results indicated that lettuce could be cultivated with up to 75% of the water requirement without significantly impacting plant development or quality. Furthermore, the investigation demonstrated that lettuce could thrive when irrigated with water of moderate salinity (1500 ppm). These findings highlight the potential for reducing water quantities and saline water in lettuce production, offering practical solutions for sustainable farming in water-scarce regions.

Nebulized Ketamine or Magnesium Sulphate for Attenuating Stress Response to Laryngoscopy and Intubation in Patients Undergoing Elective Surgeries

Nebulized Ketamine or Magnesium Sulphate for Attenuating Stress Response to Laryngoscopy and Intubation in Patients Undergoing Elective Surgeries

ZmHSFA2B self-regulatory loop is critical for heat tolerance in maize.

The growth and development of maize (Zea mays L.) are significantly impeded by prolonged exposure to high temperatures. Heat stress transcription factors (HSFs) play crucial roles in enabling plants to detect and respond to elevated temperatures. However, the genetic mechanisms underlying the responses of HSFs to heat stress in maize remain unclear. Thus, we aimed to investigate the role of ZmHSFA2B in regulating heat tolerance in maize. Here, we report that ZmHSFA2B has two splicing variants, ZmHSFA2B-I and ZmHSFA2B-II. ZmHSFA2B-I encodes full-length ZmHSFA2B (ZmHSFA2B-I), whereas ZmHSFA2B-II encodes a truncated ZmHSFA2B (ZmHSFA2B-II). Overexpression of ZmHSFA2B-I improved heat tolerance in maize and Arabidopsis thaliana, but it also resulted in growth retardation as a side effect. RNA-sequencing and CUT&Tag analyses identified ZmMBR1 as a putative target of ZmHSFA2B-I. Overexpression of ZmMBR1 also enhanced heat tolerance in Arabidopsis. ZmHSFA2B-II was primarily synthesized in response to heat stress and competitively interacted with ZmHSFA2B-I. This interaction consequently reduced the DNA-binding activities of ZmHSFA2B-I homodimers to the promoter of ZmMBR1. Subsequent investigations indicate that ZmHSFA2B-II limits the transactivation and tempers the function of ZmHSFA2B-I, thereby reducing the adverse effects of excessive ZmHSFA2B-I accumulation. Based on these observations, we propose that the alternative splicing of ZmHSFA2B generates a self-regulatory loop that fine-tunes heat stress response in maize.

Inert Gas Mild Pressure Action on Healthy Humans: The “IPA” Study

The goal of this study was to evaluate inflammatory and oxidative stress responses in human subjects (9 females and 15 males) (age [29.6 ± 11.5 years old (mean ± SD)], height [172.0 ± 10.05 cm], and weight [67.8 ± 12.4 kg]) exposed to 1.45 ATA of helium (He) or nitrogen (N2) without concurrent hyperoxia. We hypothesized that elevated gas pressures would elicit an inflammatory response concurrent with oxidative stress. Consistent with ex vivo studies, both gasses elicited neutrophil activation, small elevations in microparticles (MPs) and increases in intra-MP interleukin (IL)-1β and inflammatory nitric oxide synthase, and an increase in urinary IL-6 concurrent with a marked reduction in plasma gelsolin. Mixed responses indictive of oxidative stress, with some biomarker elevations but little change in others and a decrease in some, were observed. Overall, these results demonstrate that exposure to typical diving gasses at a mildly elevated partial pressure will initiate inflammatory responses, which may play a significant role in decompression sickness (DCS). The complex pattern of oxidative stress responses may be indicative of competing systemic reactions and sampling different body fluids.

Piwi mutant germ cells transmit a form of heritable stress that promotes longevity.

The C. elegans Argonaute protein PRG-1/Piwi and associated piRNAs protect metazoan genomes by silencing transposons and other types of foreign DNA. As prg-1 mutants are propagated, their fertility deteriorates prior to the onset of a reproductive arrest phenotype that resembles a starvation-induced stress response. We found that late-generation prg-1 mutants with substantially reduced fertility were long-lived, whereas early- or mid-generation prg-1 mutants had normal lifespans. Loss of the stress response transcription factor DAF-16 caused mid- or late-generation prg-1 mutants to live very short lives, whereas overexpression of DAF-16 enabled both mid- and late-generation prg-1 mutants to live long. Cytoplasmic P-bodies that respond to stress increased in long-lived late-generation prg-1 mutants and were transmitted to F1 but not F2 cross-progeny. Moreover, moderate levels of heritable stress shorten late-generation prg-1 mutant longevity when DAF-16 or P bodies are deficient. Together, these results suggest that the longevity of late-generation prg-1 mutants is a hormetic stress response. However, dauer larvae that occur in response to stress were not observed in late-generation prg-1 mutants. Small germ cell nucleoli that depended on germline DAF-16 were present in late-generation prg-1 mutants but were not necessary for their longevity. We propose that prg-1 mutant germ cells transmit a form of heritable stress, high levels of which promote longevity and strongly reduce fertility. The heritable stress transmitted by prg-1/Piwi mutant germ cells may be generally relevant to epigenetic inheritance of longevity.

The Effects of FR and UVA Irradiation Timing on Multi-Omics of Purple Lettuce in Plant Factories

The synergistic application of far-red (FR) and ultraviolet A (UVA) irradiation presents a promising approach for enhancing growth and the enrichment of secondary metabolites in plants. However, prolonged exposure to these combined light qualities imposes significant stress on plants, hindering their development. Therefore, an initial period of FR irradiation to promote plant growth, followed by a subsequent period of UVA irradiation to enhance the accumulation of plant quality, constitutes a viable strategy. Our study, focusing on purple lettuce, aims to elucidate the response mechanisms of the lettuce leaf under standard white light in commercial production, with the addition of different durations of FR and UVA irradiation, and to explore the complex dynamic changes at the multi-omics level. The results indicate that the duration of FR exposure is crucial in determining biomass-related phenotypes such as fresh weight, while the duration of UVA exposure significantly influences the accumulation of phenotypic markers like anthocyanins. At the transcriptional level, the most extensive transcriptional regulation was observed when FR was applied throughout the entire growth period, and UVA was applied eight days before harvest, significantly impacting pathways such as MAPK signaling cascades, plant hormone signal transduction, photosynthetic processes, and the biosynthesis of secondary metabolites. Metabolomic analysis corroborated the transcriptomic findings, with particular emphasis on antioxidant activity, photoprotection, and defense mechanisms. Our comprehensive analysis suggests that short-term UVA irradiation prior to harvest, based on full growth period FR irradiation, is feasible. The combined application of FR and UVA irradiation fine-tunes plant growth, developmental trajectories, and stress responses by modulating light signals, hormonal signals, and secondary metabolic pathways. These findings not only reveal the adaptive mechanisms of plants to fluctuating light environments but also provide a scientific basis for optimizing light management strategies in controlled plant production systems and precision agriculture.

Microscopic Modeling Techniques for Steel Fiber Reinforced Concrete: Applications and Future Directions

This article reviews micro-modeling methods for steel fiber-reinforced concrete (SFRC), including finite element, discrete element, and computational fluid dynamics approaches, to analyze its mechanical and structural behavior. The models offer predictive insights on stress response, crack propagation, and durability in SFRC, particularly in high-stress structural applications. This study discusses the limitations of current modeling practices, such as high computational demand and parameter determination challenges, and suggests future improvements to enhance simulation accuracy and scalability. This review aims to support the advancement of SFRC in structural engineering applications.

New preclinical biomarkers for prion diseases in the cerebrospinal fluid proteome revealed by mass spectrometry

Current diagnostic methods for prion diseases only work in late stages of the disease when neurodegeneration is irreversible. Therefore, biomarkers that can detect the disease before the onset of clinical symptoms are necessary. High-throughput discovery proteomics is of great interest in the search for such molecules. Here we used mass spectrometry to analyse the cerebrospinal fluid proteome in an animal prion disease: preclinical and clinical sheep affected with natural scrapie, and healthy sheep. Interestingly, we found 46 proteins in the preclinical stage that were significantly altered (p < 0.01) compared to healthy sheep, mainly associated with biological processes such as stress and inflammatory responses. Five of them were selected for validation by enzyme-like immunosorbent assay: synaptotagmin binding, cytoplasmic RNA interacting protein (SYNCRIP), involved in nucleic acid metabolism; phospholipase D3 (PLD3) and cathepsin D (CTSD), both related to lysosomal apoptosis; complement component 4 (C4), an element of the classical immune response; and osteopontin (SPP1), a proinflammatory cytokine. These proteins significantly increased in the preclinical stage and maintained their levels in the clinical phase, except for CTSD, whose concentration returned to basal levels in the clinical group. Further research is ongoing to explore their potential as preclinical biomarkers of prion diseases.

Effects of Wheel Flats on Vibration and Stress Response of the Wheel-Rail System in High-Speed Trains

With the advancement of high-speed and lightweight vehicles, the occurrence of wheel tread wear, including wheel flats, has escalated. The resulting impact loads on axle-end components and the dynamic response of the axle cannot be overlooked. On-track tests were conducted on wheel flats to obtain wheel-rail forces, axle box vibration accelerations, and axle stresses during service. Time–frequency analysis was employed to uncover patterns of variation with speed. Additionally, a dynamic model of the high-speed train–track system was developed to replicate test conditions, investigating the characteristics of wheel–rail loads and structural elastic vibrations under high-frequency excitation for various flat sizes and higher operating speeds. The findings reveal that under wheel flats, the time-domain response of the wheel–rail system exhibits periodic impacts, while the frequency-domain shows high-frequency energy comprising multiple harmonics of the wheel rotation frequency. Wheel–rail forces, axle box vibration accelerations, and axle stresses exhibit inflection points with increasing speed, particularly within the 120–160 km/h range. In the high-frequency domain, axle stresses display characteristic frequencies that remain unchanged with speed, attributed to the coupled vertical bending vibration modes of the wheel–rail system. These research results offer foundational support for predicting fatigue damage to axle-end components, assessing axle stress, and establishing tolerances for tread defect limits.

Effect of dietary Anabaena supplementation on nutrient utilization, metabolism and oxidative stress response in Catla catla fingerlings

A 60-day feeding trial was conducted to evaluate the effects of dietary Anabaena blue-green algae (ABGA) meal on the growth performance, digestibility, and physio-metabolic responses of Catla catla fingerlings (initial average weight 9.45 ± 0.15 g). Six iso-nitrogenous (30% crude protein) and iso-caloric (378.09 Kcal. digestible energy/100 g) diets were formulated: a control diet (A0, 0% ABGA) and five experimental diets with varying ABGA inclusion levels (A3: 3%, A6: 6%, A9: 9%, A12: 12%, A15: 15%). The results demonstrated that there were no significant differences (P > 0.05) in percentage weight gain (PWG), specific growth rate (SGR), protein efficiency ratio (PER), and feed conversion ratio (FCR) among the experimental groups. Additionally, dietary ABGA did not significantly affect (P > 0.05) body carcass composition among different groups. However, amylase activity significantly decreased (P < 0.05) in the A12 and A15 fed groups, whereas lipase and protease activities remained insignificant (P > 0.05) across all groups. Notably, oxidative stress responses (SOD; superoxide dismutase and CAT; catalase), carbohydrate metabolic enzymes (LDH; lactate dehydrogenase and MDH; malate dehydrogenase), and serum glucose levels increased significantly (P < 0.05) with higher ABGA inclusion. Conversely, serum albumin content significantly decreased (P < 0.05) in the ABGA-fed groups. There were no significant differences (P > 0.05) observed in serum total protein, albumin/globulin (A/G) ratio, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activities among the experimental groups. Hematological parameters revealed that RBC (red blood cell) count, hemoglobin (Hb) concentration, and packed cell volume (PCV) significantly decreased (P < 0.05), while WBC (white blood cell) count significantly (P < 0.05) increased with higher dietary ABGA inclusion. In conclusion, the inclusion of dietary ABGA up to 15% did not impair nutrient utilization and supported normal growth performance in C. catla fingerlings. However, higher inclusion levels may have a detrimental effect on their growth, nutrient utilization, and physio-metabolic responses.

Melatonin and retinal cell damage: molecular and biological functions.

The indoleamine hormone, melatonin, is produced in the pineal gland and has an essential role in many physiological functions. The pineal gland is considered to be the most important organ for producing melatonin. Nevertheless, it is important to point out that the eye is also capable of producing melatonin, and has its own circadian rhythm in producing this hormone. Melatonin is mainly produced by a subpopulation of photoreceptors in a diurnal rhythm. Numerous in vitro and in vivo studies have shown the beneficial effects of melatonin in eye-related disorders. These diseases primarily affect retinal cells, highlighting the therapeutic potential of melatonin, especially in the retina. Melatonin's ability to regulate oxidative stress response pathways and modulate the expression of antioxidant genes makes it a promising candidate for mitigating retinal cell damage. Moreover, melatonin can modulate inflammatory pathways such as NF-кB and further reduce retinal damage, as well as affecting programmed cell death such as apoptosis and autophagy in retinal cells. Therefore, the goal of this review is to explore the ways in which melatonin protects retinal cells from damage and ischemia. We discuss the mechanisms involved in order to gain valuable understanding of the possible therapeutic applications of melatonin in protection of retinal cells and treatment of retinal disorders.