The gut microbiome (GM) plays a critical role in metabolic and neurological health and is implicated in hepatic encephalopathy (HE). Chronic hyperammonemia (HA), a major contributor to cognitive and motor impairment in HE, may influence GM structure and function, yet its specific efects in GM remain unclear. Here, it was investigated how chronic HA alters the GM using a rat model fed an ammonia-enriched diet for 4 weeks. Fecal microbiota profiles obtained by 16S rRNA gene sequencing revealed marked taxonomic shifts in HA rats, with beta-diversity showing clear separation from controls. Genera within the Lachnospiraceae family and Alistipes genus were enriched in HA rats, while lactic acid-producing and xylanolytic Firmicutes were reduced. Network analysis identified Alistipes as a central node in the HA microbiome. Predicted metabolic functions were significantly altered, showing negative associations between HA and pathways related to the pyruvate dehydrogenase complex, sucrose and urea degradation, and 4-aminobutyrate (GABA) degradation. Consistent with these predictions, fecal short-chain fatty acid (SCFA) analysis revealed reduced acetic and butyric acid, alongside increased valeric and isobutyric acid levels. The predicted GABA levels increasement by GM would activate GABA receptors in immune cells and would also contribute to peripheral inflammation and, eventually, neuroinflammation. Together, these findings demonstrate that chronic HA reshapes GM composition, disrupts key metabolic pathways, and alters SCFA profiles, providing mechanistic insight into how HA- associated dysbiosis may contribute to the metabolic, immune, and neurological dysfunction characteristic of HE.

Hyperammonemia (HA) is a metabolic disorder characterized by elevated ammonia levels in the blood. Ammonia produced from the metabolism of amino acids is mainly detoxified in the liver through the urea cycle. However, defects in this cycle result in the buildup of ammonia in the blood, which is highly neurotoxic and disrupts multiple signaling pathways in the brain, including nitric oxide (NO). NO is produced from the enzyme nitric oxide synthase (NOS), which exists in three different isoforms: neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS). NO is an important signaling molecule that plays a crucial role in various physiological functions, like neurotransmission, synaptic plasticity, learning and memory, regulation of cerebral blood flow, and immune responses. The role of NO in HA pathophysiology remains debated, with evidence supporting both neurotoxic and neuroprotective effects. The present review explains the relationship between HA and different NOS isoforms in the discrete brain regions, highlighting their effects on NO production in both acute and chronic HA conditions. HA impairs the glutamate-NO-cGMP pathway through multiple mechanisms, including tonic NMDAR activation, CaMKII-mediated modulation of nNOS, neurosteroids, and neurotransmitter imbalances. Moreover, alterations in arginine transport via the y⁺LAT2 transporter, and elevated levels of methylarginine derivatives, such as asymmetric dimethylarginine, contribute to reduced NOS activity, leading to reduced NO production, increased oxidative stress, and an increased inflammatory response in HA. Understanding these multiple mechanisms underlying NOS modulation may provide new therapeutic strategies to improve neurological impairments associated with HA.

Molecular dynamics study of ammonia poisoning in proton exchange membrane with electric field

Microcystis, a commonly occurring genus of bloom-forming cyanobacteria, can produce numerous secondary metabolites, including microcystins (MCs), which are hepatotoxic and neurotoxic to humans and animals. However, the mechanisms of cyanobacterial neurotoxicity associated with MCs have not yet been clarified. This study reports the first observations of hepatic encephalopathy (HE) after exposure to Microcystis bloom extracts (MEs), which contained MCs. Mechanisms of toxicity were studied in rats exposed to MEs by use of a single intraperitoneal injection of 80μg MC-LR equivalents/kg, body mass. Abnormal serum biochemical markers of hepatic functions and histopathological damage of liver and cerebral cortex were observed. Specifically, Alzheimer type II astrocytes, histological markers of HE, were observed. Motor impairment and significantly increased concentrations of ammonia in serum, increased activities of glutamine synthetase, and concentrations of glutamine in the cerebral cortex were detected, which indicated occurrence of HE. Mechanisms of HE, including ammonia poisoning, oxidative stress and inflammation, were confirmed by real-time quantitative PCR and transcriptomics. Also, transcriptomics revealed that zinc ions dyshomeostasis and ferroptosis are involved in the development of HE. This study presents novel insights into neurotoxic symptoms in human poisonings caused by Microcystis, links neurotoxicity in the brain to the liver, i.e., the liver-brain axis, and provides a new perspective on the multi-organ toxicity of Microcystis and a basis for developing treatments.

Sargassum fusiforme improves the growth conditions of prawn by means of nutrient utilization and improvement of the microbial environment.

Transplanting Cetobacterium can alleviate acute ammonia intoxication by promoting the synthesis of ornithine of yellow catfish

The quality of water is the main consideration to the sustainability, production, and wellbeing of aquatic animal farming systems. Traditional manual monitoring systems tend to be insufficient to identify high rate and damaging environmental changes which results in low growth outcomes, epidemics and high stock wastages. This paper outlines the design, development, and experimental research of an Internet of Things (IoT)-based water quality and habitat monitoring solution that is expected to monitor and secure the creation of stable and healthy aquatic systems. The suggested system is an autonomous system that monitors essential physicochemical conditions of the surrounding such as dissolved oxygen, pH, temperature, turbidity, concentration of ammonia, etc with a collection of low-cost and high-precise sensors connected to an edge-processing microcontroller unit. The obtained data are sent in the real-time mode to a cloud-based solution to be constantly visualised, stored, and generate automatic alerts as unsafe threshold rates are found. The system was implemented and experimented in several freshwater aquaculture ponds with a period of operations of 90 days. The experimental outcomes show that the stability of the water quality levels have improved significantly with few instances of hypoxic conditions, ammonia poisoning and spikes in turbidity. Significant mortality rates of nearly 20-30% in aquatic animals were also reduced as compared to the ponds that were under traditional management indicating that priority measures in detecting stress and prompt corrective measures were effective. Also, the system enhanced efficiency concerning resources since it facilitated efficient aeration and water exchange schedules. Its results verify that digital monitoring based on IoT creates a credible, scalable and cost-effective answer to smart aquaculture prohibition. The suggested system should add value to the development of sustainable and intelligent fish-farming due to its higher levels of environmental control, reduction of the ecological risks, and animal welfare.

BackgroundAmmonia generated from amino acid metabolism is a cytotoxin that can adversely affect cell function and overall health and potentially lead to cellular toxicity and death due to its accumulation. Previous studies have shown that acute ammonia intoxication (AI) can increase the intestinal C. somerae abundance, hinting at a possible involvement of C. somerae in the host's reaction to AI. Nonetheless, the precise mechanism through which C. somerae mitigates the effects of AI is uncertain.ResultsThis research elucidated the metabolic mechanism of transplanting Cetobacterium somerae ceto (CSC) to assist the host in managing AI. Our results suggest that (I) AI resulted in impaired ureagenesis pathway. This was manifested by elevated levels of ammonia in the blood, liver, and intestines, along with decreased urea levels. (II) Supplementing orally with live CSC facilitated its colonization in the intestines, mitigating AI by reversing depletion of intestinal argininosuccinic acid (ARA) and promoting ureagenesis. (III) CSC synthesized ARA from aspartate and asparagine through the asnA-ansA/B-argG gene cluster. Additionally, CSC assimilated fumaric acid and malic acid from the environment, dampening the degradation of ARA by CSC’s fumA-fumB-argH gene cluster. (IV) Live CSC provided ARA support for ureagenesis in the intestine and liver, reducing endogenous ammonia levels of pseudo-sterile yellow catfish. (V) Supplementation of ARA decreased systemic ammonia levels by promoting ureagenesis. Inhibiting the expression of argininosuccinate lyase in the liver through RNA interference can impede arginine synthesis, thereby eliminating the ammonia-lowering effect of ARA.ConclusionIn summary, this study found that the role of probiotics in enhancing the host's resistance to AI depends on the function of ARA generated by CSC. AI can lead to depletion of ARA and interrupting ureagenesis, while CSC-produced ARA supplements ureagenesis in the liver and intestines, facilitating ammonia detoxification into urea.3nXfo9ChTCkCwihH-W8hdsVideo

Ammonia serves as a viable alternative among hydrogen carriers, offering numerous advantages such as low production costs, global availability, established production and storage infrastructure, ease of liquefaction under mild conditions, and high volumetric energy density. However, the process of extracting hydrogen via ammonia cracking demands substantial energy, hence demanding the development of energy conversion devices that directly utilize ammonia as a fuel source. Among these, anion exchange membrane fuel cell (AEMFCs) have garnered recent interest for their ability to employ ammonia as a fuel through the ammonia oxidation reaction in an alkaline environment. Despite their potential, the direct use of ammonia in AEMFCs, rather than hydrogen, markedly decreases the catalytic activity, leading to inferior performance. To address this challenge, enhancing the performance of direct ammonia fuel cell (DAFCs), three critical components of the membrane-electrode assembly are necessary: 1) a highly active anode catalyst, 2) an anion exchange membrane that minimizes ammonia crossover, and 3) a cathode catalyst that mitigates ammonia poisoning. In this study, we present an optimized electrode configuration integrating these key components to achieve high performance in DAFCs.

Valproic acid (VPA) use is associated with an increased risk of hyperammonemia (HA); however, the specific interactions between HA risk factors in VPA-treated patients remain unclear. This study aimed to identify and assess the effects of multiple interactions between different risk factors affecting HA to improve clinical risk stratification in patients undergoing VPA therapy. We conducted a retrospective cohort study by reviewing the medical records of patients treated with VPA at a single center from January 2019 to December 2021. The SHapley Additive exPlanations (SHAP) method was used to interpret model predictions, revealing the relative importance and interactions of factors affecting HA risk. SHAP interaction scores were used to assess the effects of multiple interactions between features, providing a comprehensive analysis of how risk factors interact. This study identified the Top 15 predictors of HA, ranked by importance: patient age, VPA blood concentration, VPA dose, epilepsy, VPA treatment duration, levetiracetam use, hypertension, mental disorders, and number of medications. Notable multiple interaction effects were observed, particularly between age and factors including VPA concentration, epilepsy, and treatment duration. Younger patients and those with elevated VPA concentrations were at increased risk of developing HA, especially when epilepsy or polypharmacy were present. This study highlights several critical factors potentially influencing HA development in VPA-treated patients, particularly younger patients, those with epilepsy, or those undergoing polypharmacy. However, as a single-center retrospective study, these findings necessitate further validation through additional research.

Among chemotherapy-related adverse events, drug-induced liver injury (DILI) is one of the most prevalent. In some cases, DILI is accompanied by hyperammonaemia (HA), which can disrupt chemotherapy cycles, and is associated with 25–45% mortality rates when specific antitumor agents are used. Efficacy studies in cancer patients were only found for ornithine (L-ornithine L-aspartate, LOLA) among all ammonia-lowering strategies. The amino acids in LOLA help to detoxify ammonia in the liver and other tissues, while also having several other metabolic effects. The experts expressed their viewpoints on the conducted studies, reviewed the main directions for applying LOLA in current clinical practice, and identified prospects for further research.

Phytotesting of soils with traditional and new forms of nitrogen fertilizers was carried out in the laboratory at the D.N. Pryanishnikov All-Russian Research Institute of Agrochemistry in 2024-2025. Prolonged-release urea-formaldehyde fertilizers (UF), which contain fast- and slow-soluble nitrogen, were tested. The length of the roots of spring wheat and white mustard seedlings in sod-podzolic soil and leached chernozem after composting fertilizers for 28 and 50 days was estimated. When applying conventional carbamide, regardless of the type of soil and crop, with an increase in the composting period, a stronger inhibition of plant root growth was observed. The decomposition products of fertilizers had a less pronounced negative effect on white mustard. In general, according to experience, the phytotoxicity of UFs was lower compared to standard carbamide, as well as lower in leached chernozem compared to sod-podzolic soil. The stimulating effect of prolonged forms of nitrogen fertilizers during prolonged composting was revealed in the chernozem on white mustard plants by 9; 63 and 137%, respectively, and on UF-3 spring wheat plants by 28%. The study of the dynamics of fertilizer conversion showed that the content of ammonium nitrogen in the soil decreased to the initial level on the 21st day and ammonia poisoning could not cause phytotoxicity. It is shown that the accumulation of nitric acid as a result of nitrification led to significant acidification of the soil. In the carbamide variant, on days 21-28, there was a more pronounced decrease in the reaction of the soil environment to the pHKCl to 4.6-4.7 units, which is 0.6-0.7 units. lower than in the original soil, when applying UFs, the pHKCl was significantly higher and amounted to 4.9-5.0 units.

Ammonia (NH3), a harmful gas, reduces livestock productivity, threatens their health, and causes economic losses. Luteolin (Lut), an anti-inflammatory flavonoid, may counteract these effects. Our study explored luteolin's protective mechanisms on chicken splenic lymphocytes under ammonia stress using a simulation model and four-dimensional fast data-independent acquisition (4D-FastDIA) proteomics. We identified 316 proteins, with 69 related to ammonia's negative effects and 247 to Lut's protection. Thirty differentially expressed proteins (DEPs) were common to both groups, with 27 showing counter-regulation with Lut. Gene Ontology (GO) analysis showed DEPs enriched in molecular responses to interferons and the negative regulation of immune responses, mainly located extracellularly. Molecular function analysis revealed DEPs in antigen binding and synthase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis linked DEPs to pathways like estrogen signaling, NOD-like receptor signaling, cytokine-cytokine receptor interaction, and JAK-STAT signaling. The quantitative real-time polymerase chain reaction (qRT-PCR) results indicated that the mRNA levels of Interferon Alpha and Beta Receptor subunit 2 (IFNAR2) and Signal Transducer and Activator of Transcription 1 (STAT1) were trending downward. This observation was in strong agreement with the downregulation noted in the proteomics analysis. Lut's protective role against ammonia's adverse effects on chicken splenic lymphocytes is linked to the modulation of key signaling pathways, offering insights for further research on treating ammonia exposure with Lut.

Ammonia poisoning is a common issue in fish breeding systems, leading to complications such as hypoxia and cellular energy crises. The AMP-deaminase enzyme plays a crucial role in maintaining the ATP/AMP ratio and responding to energy deficits. This study investigates the adaptation of AMP-deaminase in Asian sea bass (Lates calcarifer) to ammonia stress. A total of 150 fish were divided into two groups with densities of 6g/L (control) and 14g/L (densely stock fish), each replicated three times over 60days. Ammonia levels increased significantly in both groups (P < 0.0001), with a higher concentration in the densely stock fish (> 1.6-fold increase compared to control, P < 0.001). The enzyme activity showed a significant enhancement in the densely stock fish, with Kcat increasing from 1.85 to 2.70 S-1 and Vmax decreasing from 11.99 to 8.10μmol/mg s. The enzyme's stability was significantly higher in adverse conditions, as evidenced by an extended half-life (7 vs. 6days in control, P < 0.05) and increased resistance to urea denaturation (I50 at 1.6mM vs. 0.8mM in control, P < 0.01). Optimal pH shifted from 7 (control) to 6 (densely stocked fish, P < 0.05), indicating an adaptation to acidic conditions. Additionally, enzyme activity remained stable under oxidative stress (H2O2 + FeSO4 exposure) and exhibited a significantly lower activation energy in the densely stock fish (14.1 vs. 17.98kJ/mol, P < 0.05). These findings indicate that the AMP-deaminase enzyme in Lates calcarifer adapts to ammonia-induced hypoxia by modifying its kinetic properties and structural stability, enhancing muscle resilience under environmental stress. Further genetic and metabolic studies will strengthen these findings.

ABSTRACTAmmonia (NH₃) is a crucial industrial chemical used mostly in agriculture, with a global production of approximately 150 million metric tons by 2023. Despite its significance, ammonia manufacturing poses significant safety risks because of its high pressure, hydrogen content, and potential for hazardous accidents. To improve the safety analysis of ammonia synthesis, this study uses a dynamic simulation with Honeywell UniSim Design software. The simulation models the dynamic behavior of a 1000 TPD ammonia synthesis loop, based on the Haber‐Bosch process, at the Fertilizers and Chemicals Travancore Limited plant in Udyogamandal, Kerala, India. This study evaluated two primary risk scenarios: leakage in the ammonia synthesis pipeline and abnormal liquid levels in the ammonia separator, using dynamic simulation‐based Hazard and Operability Analysis (HAZOP). These results suggest that high liquid levels in the separator can cause liquid ammonia entrainment, compressor failure, and toxic leakage in the event of equipment failure. The pipeline leakage study points out the possibility of explosions and ammonia poisoning, with ammonia concentrations exceeding hazardous levels within minutes. This dynamic simulation‐based method provides important insights for process safety management in industrial ammonia production by better identifying risks and quantifying safety concerns than traditional steady‐state models.

High-alkalinity water bodies can disrupt normal ammonia metabolism in fish, leading to ammonia poisoning. In China, there exists a highly tolerant group of Amur ide (Leuciscus waleckii) that can survive in extreme alkaline lakes with alkalinity up to 53.57 mM (pH 9.6), making it an excellent model for elucidating the high-alkalinity tolerance mechanism in fish. We have discovered that this species has evolved a special ammonia excretion mechanism to maintain ammonia efflux in high-alkalinity environments. Compared to the freshwater forms of Amur ide, the ammonia excretion protein RHBG plays a prominent role in the ammonia excretion process of the alkali forms of Amur ide; however, the regulatory mechanism of RHBG expression in fish remains unclear. Through DNA pull-down, RNA-Seq, qPCR, Western blotting, immunofluorescence, and dual-luciferase reporter assays, this study demonstrates that the transcription factor HIF1A can inversely regulate the expression of Rhbg by binding to its promoter region, thereby participating in the high-alkalinity adaptation process of fish. The findings of this study provide a theoretical basis for elucidating the ammonia excretion mechanism and revealing the alkalinity tolerance mechanism in fish.

The current study attempted to establish Yucca schidigera extract (YSE) modifying effects on long-term ammonia (NH 3 ) poisoning in Nile Tilapia. Randomly, 300 Nile tilapia fish were divided into 5 equal groups, each including four replications. One group was retained as the standard control (1 st ) group, and the 2 nd group was subjected to NH 3 for three weeks (during the last week of the 1 st , 2 nd and 3 rd month of the experiment), and the 3 rd , 4 th and 5 th groups were supplemented with YSE (6, 8 and 10 mg/L water every 2 days) and subjected to NH 3 for three weeks (during the last week of the 1 st , 2 nd and the 3 rd month of the experiment), respectively. A significant improvement in water quality was recorded with YSE by increasing dissolved oxygen in the water and decreasing water pH, total ammonia nitrogen concentration, and un-ionized ammonia. Feed intake and feed conversion were improved with all groups supplemented with YSE. YSE supplementation to ammonia-polluted water of Nile tilapia significantly improved liver and kidney functions such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatinine, urea, and uric acid. YSE improved immunity and antioxidant parameters when compared to the ammonia group. Digestive enzymes were enhanced by the addition of YSE to the ammonia-polluted water of Nile tilapia. In conclusion, our investigation aimed to declare YSE modulatory effects on the quality of water, growth performance, immunological status, and antioxidant capacity in fish. • YSE has potential growth-promoting, antimicrobial, and immunostimulant effects for several fish species. • Yucca schidigera extract improved the performance and health of fish. • Digestive enzymes specially lipase and amylase improved by YSE supplementation. • YSE has a good role in mitigating the negative impact of ammonia intoxication.

Valproic acid, frequently prescribed for neurological and psychiatric disorders, can cause hyperammonemia (HA). This retrospective study aimed to investigate the association among the basic characteristics, comorbidities, co-medications, and risk of HA in patients receiving valproic acid. We compared groups with and without HA using data collected from the medical records of adults undergoing valproic acid monitoring between January 1, 2019, and December 31, 2021. We conducted a multivariable logistic regression analysis to explore the risk factors for HA and a comprehensive systematic literature review to identify factors significantly associated with valproic acid-related HA. In total, 247 patients were included, with 37 in the HA group (serum ammonia level >150 mcg/dL); almost all of them eventually developed hyperammonemic encephalopathy (HE). Multivariable logistic regression analysis revealed that valproic acid levels (odds ratio (OR): 1.01, 95% confidence interval (CI): 0.99-1.03), epilepsy (OR: 3.82, 95% CI: 1.52-9.62), congestive heart failure (OR: 32.3, 95% CI: 4.09-255.4), and concomitant phenytoin use (OR: 6.4, 95% CI: 1.07-38.12) are independently associated with HA development during valproic acid therapy. Our data and those of previous studies demonstrate significant associations of valproic acid-related HA with concomitant phenytoin and topiramate use; serum valproic acid concentrations were also significantly positively correlated with serum ammonia levels. The results suggest that serum ammonia and valproic acid levels should be monitored during valproic acid treatment, particularly with concurrent use of phenytoin or topiramate, to prevent further deterioration of HE.

Luteolin-mediated phosphoproteomic changes in chicken splenic lymphocytes: Unraveling the detoxification mechanisms against ammonia-induced stress.

Two different diets able to induce dietary hyperammonaemia (a methionine-choline-deficient (MCD) diet and a methionine-deficient diet enriched with ammonium acetate (MAD + 20% ammonium acetate)) were tested in a rat model. The diets were shown to have different modes of action, inducing significant hyperammonaemia (HA) and growth retardation in the rats, with different metabolic consequences. The MCD diet resulted in the development of endogenous HA, with a decrease in bilirubin levels and an increase in hepatic fat content. In contrast, the MAD + 20% ammonium acetate diet increased circulating ALP and haptoglobin levels and decreased liver mass. The above results suggest that the MCD diet deteriorated the liver function of the rats, resulting in the development of endogenous HA, while the MAD diet caused moderate changes in liver metabolism, resulting in the development of exogenous HA. Interestingly, the commonly used oral treatments Lactulose and Rifaximin did not ameliorate hyperammonaemia during or after the treatment period. In conclusion, even though the diets used in the current study caused somewhat similar hyperammonaemia, they seemed to provoke different metabolic consequences. The latter can have an impact on the severity of the resulting hyperammonaemia and thus on the hyperammonaemia-induced encephalopathy, resulting in the development of distinguishing cognitive and metabolic (liver) effects compared to other forms of encephalopathy. We hypothesized that these rat models, with significantly increased serum ammonia levels, along with different liver injuries, could serve as a suitable double animal model for the testing of new, oral enzyme therapies for hepatic encephalopathy in future studies.