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1.
J Comp Physiol B ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39237834

ABSTRACT

Energy conservation associated with hibernation is maximized at the intersection of low body temperature (Tb), long torpor bouts, and few interbout arousals. In the arctic ground squirrel (Urocitellus parryii), energy conservation during hibernation is best achieved at ambient temperatures (Ta) around 0 °C; however, they spend the majority of hibernation at considerably lower Ta. Because arctic ground squirrels switch to mixed fuel metabolism, including protein catabolism, at extreme low Ta of hibernation, we sought to investigate how microbial urea-nitrogen recycling is used under different thermal conditions. Injecting squirrels with isotopically labeled urea (13C/15N) during hibernation at Ta's of - 16 °C and 2 °C and while active and euthermic allowed us to assess the ureolytic activity of gut microbes and the amount of liberated nitrogen incorporated into tissues. We found greater incorporation of microbially-liberated nitrogen into tissues of hibernating squirrels. Although ureolytic activity appears higher in euthermic squirrels, liberated nitrogen likely makes up a smaller percentage of the available nitrogen pool in active, fed animals. Because non-lipid fuel is a limiting factor for torpor at lower Ta in this species, we hypothesized there would be greater incorporation of liberated nitrogen in animals hibernating at - 16 °C. However, we found higher microbial-ureolytic activity and incorporation of microbially-liberated nitrogen, particularly in the liver, in squirrels hibernating at 2 °C. Likely this is because squirrels hibernating at 2 °C had higher Tb and longer interbout arousals, a combination of factors creating more favorable conditions for gut microbes to thrive and maintain greater activity while giving the host more time to absorb microbial metabolites.

2.
Hum Immunol ; 85(6): 111092, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39255559

ABSTRACT

PURPOSE: The objective of this research is to analyze the clinical progression and identify prognostic factors among elderly patients with sepsis admitted to the emergency intensive care unit (EICU). METHODS: A total of 211 patients with sepsis, aged 65 years or above, were selected for inclusion in the study. These patients were admitted to the EICU of the Emergency Department at Harrison International Peace Hospital Affiliated to Hebei Medical University from August 2018 to June 2023. The clinical features, Acute Physiology and Chronic Health Evaluation (APACHE) Π score, Sequential Organ Failure Assessment (SOFA) score, and routine laboratory test indicators were documented. All patients were followed up for 28 days. The factors associated with mortality in both the sepsis group and septic shock group were analyzed by receiver operating characteristic (ROC) curve, MedCalc software, and Kaplan-Meier curve. RESULTS: Among the 211 patients, 101 were identified as having septic shock. A significant elevation in blood urea nitrogen-to-albumin ratio (BAR) and inflammatory indicators, APACHE II score, and SOFA score was observed in the septic shock group compared to the sepsis group (P<0.001). Moreover, the sepsis group exhibited a higher proportion of males (P=0.002), while there was no statistically significant difference in age (P=0.467). Further analysis revealed that BAR within 24 h after admission exhibited a positive correlation with infection indicators procalcitonin (PCT) and C-reactive protein (CRP), as well as disease severity scores APACHE Π and SOFA. Additionally, BAR was found to be positively associated with the 28-day mortality rate in patients with sepsis (r = 0.169, P=0.001). The results of the ROC curve analysis showed that BAR exhibited the highest predictive capability for 28-day mortality in elderly patients with sepsis who were admitted to the EICU (AUC=0.614). The Kaplan-Meier survival curve, which identified the optimal cut-off value (≥0.3) of BAR as the most accurate predictor of 28-day mortality in this individual, revealed a significantly higher mortality rate among patients with BAR≥0.3 (χ2 = 12.340, P=0.000). CONCLUSION: The elderly patients with sepsis in the EICU are generally over the age of 70, with a higher prevalence of males than females, and the albumin level is generally low on admission. Furthermore, BAR is significantly and positively correlated with infectious indexes and has a high predictive value for their mortality outcomes.

3.
Ital J Pediatr ; 50(1): 171, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39256843

ABSTRACT

BACKGROUND: This study aimed to investigate the clinical and molecular genetic characteristics of ten children with ornithine carbamoyltransferase deficiency (OTCD) in southeastern China, as well as the correlation between the genotype and phenotype of OTCD. METHODS: A retrospective analysis was performed on the clinical manifestations, laboratory testing, and genetic test findings of ten children with OTCD admitted between August 2015 and October 2021 at Quanzhou Maternity and Children's Hospital of Fujian Province in China. RESULTS: Five boys presented with early-onset symptoms, including poor appetite, drowsiness, groaning, seizures, and liver failure. In contrast, five patients (one boy and four girls) had late-onset gastrointestinal symptoms as the primary clinical manifestation, all presenting with hepatic impairment, and four with hepatic failure.Nine distinct variants of the OTC gene were identified, including two novel mutations: c.1033del(p.Y345Tfs*50) and c.167T > A(p.M56K). Of seven patients who died, five had early-onset disease despite active treatment. Three patients survived, and two of them underwent liver transplantation. CONCLUSIONS: The clinical manifestations of OTCD lack specificity. However, elevated blood ammonia levels serve as a crucial diagnostic clue for OTCD. Genetic testing aids in more accurate diagnosis and prognosis assessment by clinicians. In addition, we identified two novel pathogenic variants and expand the mutational spectrum of the gene OTC, which may contribute to a better understanding of the clinical and genetic characteristics of OTCD patients.


Subject(s)
Ornithine Carbamoyltransferase Deficiency Disease , Humans , Male , Female , China , Retrospective Studies , Ornithine Carbamoyltransferase Deficiency Disease/genetics , Ornithine Carbamoyltransferase Deficiency Disease/diagnosis , Infant , Ornithine Carbamoyltransferase/genetics , Child, Preschool , Genetic Testing , Mutation , Phenotype
4.
Angew Chem Int Ed Engl ; : e202410105, 2024 Sep 07.
Article in English | MEDLINE | ID: mdl-39243195

ABSTRACT

The direct coupling of nitrate ions and carbon dioxide for urea synthesis presents an appealing alternative to the Bosch-Meiser process in industry. The simultaneous activation of carbon dioxide and nitrate, however, as well as efficient C-N coupling on single active site, poses significant challenges. Here, we propose a novel metal/hydroxide heterostructure strategy based on synthesizing an Ag-CuNi(OH)2 composite to cascade carbon dioxide and nitrate reduction reactions for urea electrosynthesis. The strongly coupled metal/hydroxide heterostructure interface integrates two distinct sites for carbon dioxide and nitrate activation, and facilitates the coupling of *CO (on silver, where * denotes an active site) and *NH2 (on hydroxide) for urea formation. Moreover, the strongly coupled interface optimizes the water splitting process and facilitates the supply of active hydrogen atoms, thereby expediting the deoxyreduction processes essential for urea formation. Consequently, our Ag-CuNi(OH)2 composite delivers a high urea yield rate of 25.6 mmol gcat.-1 h-1 and high urea Faradaic efficiency of 46.1%, as well as excellent cycling stability. This work provides new insights into the design of dual-site catalysts for C-N coupling, considering their role on the interface.

5.
Cureus ; 16(8): e66148, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39233985

ABSTRACT

Upendranath Brahmachari (1873-1946) was a prominent Indian scientist and physician renowned for his groundbreaking work in tropical medicine. He is most famous for discovering urea stibamine, a highly effective treatment for kala-azar (visceral leishmaniasis), a deadly parasitic disease. This discovery had a significant impact on public health, saving countless lives in India and beyond. Born in Jamalpur, Bihar, Brahmachari pursued medical education at the University of Calcutta, where he later became a professor. His dedication to medical science earned him numerous accolades, including a knighthood in 1934. In 1929, Brahmachari was nominated for the Nobel Prize in Physiology or Medicine in recognition of his work on urea stibamine. Although he did not win, the nomination underscored the global significance of his contributions. In addition to his scientific achievements, Brahmachari was active in public service, advocating for improved healthcare and medical education in India. His legacy continues to inspire medical professionals and researchers worldwide.

6.
Article in English | MEDLINE | ID: mdl-39258713

ABSTRACT

Urea electrolysis can address pressing environmental concerns caused by urea-containing wastewater while realizing energy-saving hydrogen production. Highly efficient and affordable electrocatalysts are indispensable for realizing the great potential of this emerging technology. Among the numerous candidates, α-Ni(OH)2 has the merits of good electrocatalytic activity, adjustable heteroelement doping, and low cost; consequently, it has received tremendous attention in the electrolytic fields. Herein, a Y3+-doping strategy is developed to effectively enhance the catalytic performance of nickel hydroxide in the urea oxidation reaction (UOR). Our results show that Y3+ incorporation successfully modulates the electronic structure of α-Ni(OH)2 by inducing Ni3+ formation in the crystal lattice to initiate direct UOR, facilitates the Ni3+/Ni2+ redox transition with higher current responses to promote indirect UOR, and maintains the structural stability of YNi-10 (Ni2+/Y3+ molar ratio = 1:0.1) during long-term UOR operation. Owing to these features, the obtained YNi-10 sample exhibits a higher current density (127 vs 79 mA cm-2 at 1.5 V), a lower Tafel slope (48 vs 75 mV dec-1), a larger potential difference between the UOR and oxygen evolution reaction (OER, 0.26 vs 0.22 V at 80 mA cm-2), a higher reaction rate constant (1.1 × 105 vs 3.1 × 103 cm3 mol-1 s-1), and a reduced activation energy of UOR (2.9 vs 14.8 kJ mol-1) compared with the Y-free counterpart (YNi-0). This study presents a promising strategy to simultaneously boost direct and indirect UORs, providing new insights for further developing high-performance electrocatalysts.

7.
Adv Mater ; : e2409292, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39221668

ABSTRACT

Gas-evolving reactions (GERs) are important in many electrochemical energy conversion technologies and chemical industries. The operation of GERs at high current densities is critical for their industrial implementation but remains challenging as it poses stringent requirements on the electrodes in terms of reaction kinetics, mass transfer, and electron transport. Here the general and rational design of self-standing carbon electrodes with vertically aligned porous channels, appropriate pore size distribution, and high surface area as supports for loading a variety of catalytic species by facile electrodeposition are reported. These electrodes simultaneously possess high intrinsic activity, large numbers of active sites, and efficient transport highways for ions, gases, and electrons, resulting in significant performance improvements at high current densities in diverse GERs such as urea oxidation, hydrogen evolution, and oxygen evolution reactions, as well as overall urea/water electrolyzers. As an example, the carbon electrode decorated with Ni(OH)2 demonstrates a record-high current density of 1000 mA cm-2 at 1.360 V versus the reversible hydrogen electrode, largely outperforming the conventional nickel foam-based counterpart and the state-of-the-art electrodes.

8.
Adv Mater ; : e2409697, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39221670

ABSTRACT

Electrocatalytic C-N coupling between NO3 - and CO2 has emerged as a sustainable route for urea production. However, identifying catalytic active sites and designing efficient electrocatalysts remain significant challenges. Herein, the synthesis of Cu-doped MnO2 nanotube (denoted as Cu-MnO2) with stable Cuδ+-oxygen vacancies (Ovs)-Mn3+ dual sites is reported. Compared with pure MnO2, Cuδ+ doping can effectively enhance urea production performance in the co-reduction of CO2 and NO3 -. Thus, Cu-MnO2 catalyst exhibits a maximum Faradaic efficiency (FE) of 54.7% and the highest yield rate of 116.7 mmol h-1 gcat. -1 in a flow cell. Remarkably, the urea yield rate remains over 78 mmol h-1 gcat. -1 across a wide potential range. Further experimental and theoretical results elucidate the unique role of Cu-MnO2 solid-solution for stabilizing Cuδ+ sites in Cuδ+-Ovs-Mn3+, endowing the catalyst with superior structural and electrochemical stabilities. This thermodynamically promotes urea formation and kinetically lowers the energy barrier of C-N coupling.

9.
Nano Lett ; 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39248551

ABSTRACT

The atomic defect engineering could feasibly decorate the chemical behaviors of reaction intermediates to regulate catalytic performance. Herein, we created oxygen vacancies on the surface of In(OH)3 nanobelts for efficient urea electrosynthesis. When the oxygen vacancies were constructed on the surface of the In(OH)3 nanobelts, the faradaic efficiency for urea reached 80.1%, which is 2.9 times higher than that (20.7%) of the pristine In(OH)3 nanobelts. At -0.8 V versus reversible hydrogen electrode, In(OH)3 nanobelts with abundant oxygen vacancies exhibited partial current density for urea of -18.8 mA cm-2. Such a value represents the highest activity for urea electrosynthesis among recent reports. Density functional theory calculations suggested that the unsaturated In sites adjacent to oxygen defects helped to optimize the adsorbed configurations of key intermediates, promoting both the C-N coupling and the activation of the adsorbed CO2NH2 intermediate. In-situ spectroscopy measurements further validated the promotional effect of the oxygen vacancies on urea electrosynthesis.

10.
Chemistry ; : e202402536, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39250167

ABSTRACT

For the first time, explicit stabilization of all the three conformers, viz. (cis,cis), (cis,trans) and (trans,trans), of a 'nano-sized' highly-flexible urea-bridged Zn(II)porphyrin dimer have been achieved via careful manipulations of external stimuli such as solvent dielectrics, temperature, anionic interactions, axial ligation and surface-induced stabilization. The conformers differ widely in their structures, chemical and photophysical properties and thus have vast potential applicability. X-ray structural characterizations have been reported for the (cis,cis) and (cis,trans)-conformers. While (cis,cis) conformer stabilized exclusively in dichloromethane, more polar solvents resulted in the stabilization of (cis,trans) and (trans,trans)-conformers. Low temperature promotes the stabilization of (cis,trans)-conformer while rise in temperature facilitates flipping to the (cis,cis) one. Significantly, exclusive stabilization of the (trans,trans)-isomer has been illustrated using acetate anion which facilitates H-bonding with the two amide linkages of the urea spacer. Remarkably, HOPG surface facilitates stabilization of the energetically challenging (trans,trans)-conformer via CH···p and p···p interactions with the solid surface to the porphyrinic cores. DFT calculations demonstrate that the relative stability of the conformers can be modulated upon slight external perturbations as also observed in the experiment. Several factors contributing towards the conformational landscape for the highly flexible urea-bridged porphyrin dimers have been mapped.

11.
Int J Biol Macromol ; : 135364, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39245120

ABSTRACT

An ion exchange nanofiber membrane (AEA-COOH) was developed from polyacrylonitrile (PAN) nanofibers through chemical hydrolysis. It was further modified by grafting chitosan (CS) onto its surface, creating the AEA-COOH-CS membrane. Then, both membranes were covalently immobilized with imidazolidinyl urea (IU), resulting in AEA-COOH-IU and AEA-COOH-CS-IU membranes. This study analyzed their physical properties, antibacterial efficacy (AE), and reusability. Optimal conditions were identified: 50 kDa molecular weight of chitosan, pH 8 for IU modification, and 0.05 % IU concentration. The AEA-COOH-IU membrane achieved 96.15 % AE against Escherichia coli at an initial concentration of 2.0 × 107 CFU/mL, while the AEA-COOH-CS-IU membrane achieved 100 % AE. The AEA-COOH-CS-IU membrane maintained 95.04 % efficacy over 5 cycles, demonstrating superior durability. As a result, the AEA-COOH-CS-IU membrane has high potential for environmental applications such as water purification and wastewater treatment. Its robust antibacterial properties and reusability suggest a significant impact on ensuring cleaner water resources and prospective uses in the biomedical field, including medical device coatings and healthcare applications.

12.
Heliyon ; 10(16): e36003, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39220945

ABSTRACT

Introduction: To date, newborn screening (NBS) for proximal urea cycle disorders, including Ornithine transcarbamylase deficiency (OTCD), was not recommended due to the lack of appropriate tests and insufficient evidence of the benefits. This study aimed to investigate the potential of tandem mass spectrometry (MS/MS) for OTCD screening and its value in guiding further investigation to obtain a final diagnosis in high-risk patients. Methods: The study included patients with OTCD referred to the National Children's Hospital between April 2020 and November 2023. A retrospective evaluation of amino acid concentrations measured by MS/MS and their ratios in patients with early-onset and late-onset OTCD was conducted. Results: While all ten early-onset cases had glutamine concentrations above the upper limit, only five of them had citrulline concentrations below the lower limit of the reference interval. Only two late-onset cases had elevated glutamine levels, while all had citrulline within reference intervals. The Cit/Phe ratio was decreased, and the Gln/Cit and Met/Cit ratios were increased in all early-onset OTCD cases, while they were abnormal in only one late-onset case. Conclusions: The preliminary results suggest that hyperglutaminemia, in combination with low or normal citrulline concentrations and specific ratios (Gln/Cit, Met/Cit, and Cit/Phe), can serve as reliable markers for screening early-onset OTCD in high-risk patients. However, these markers proved less sensitive for detecting the late-onset form, even in symptomatic patients.

13.
Cureus ; 16(8): e65956, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39221296

ABSTRACT

Ornithine transcarbamylase deficiency (OTCD) is the most common subtype of urea cycle disorders. Caused by mutations in the X-linked gene OTC,it often leads to hyperammonemia which can result in neurotoxicity, coma, and death. We describe the clinical course of a male newborn known to carry a hypomorphic variant (p.Leu301Phe) in OTC previously reported in cases with later-onset OTCD. Despite being clinically asymptomatic, our affected patient presented with hyperammonemia in the neonatal period. Oral feedings were temporarily discontinued, and low protein medical formula and ammonia scavenger medications were initiated to normalize ammonia levels. This case supports the pathogenicity of the reported OTC gene variant and early presentation that necessitates disease-specific management. Our report will help provide guidance surrounding the most appropriate management of future patients with this variant as they will likely require management in the newborn period.

14.
J Perianesth Nurs ; 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39217526

ABSTRACT

Argininemia is a rare autosomal recessive metabolic disorder characterized by a deficiency of arginase, a vital enzyme in the urea cycle. This metabolic defect results in the accumulation of arginine and its metabolites, leading to hyperammonemia and associated neurological symptoms. We present a case detailing the perioperative management of an 11-year-old male child diagnosed with argininemia undergoing circumcision. The perioperative management of patients with argininemia presents unique challenges due to the risk of hyperammonemia and neurological decompensation triggered by physiological stress, fasting, and the catabolic state associated with surgery. This case report highlights the importance of individualized anesthetic strategies for patients with rare metabolic disorders like argininemia. A multidisciplinary approach involving collaboration among anesthesiologists, endocrinologists, dietitians, and surgeons is essential to ensuring a safe perioperative experience for these patients. Further research is essential to refine perioperative protocols and optimal anesthetic interventions for individuals with argininemia undergoing surgical procedures.

15.
Carbohydr Polym ; 344: 122523, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39218546

ABSTRACT

Cellulose laminates represent a remarkable convergence of natural materials and modern engineering, offering a wide range of versatile applications in sustainable packaging, construction, and advanced materials. In this study, novel all-cellulose laminates are developed using an environmentally friendly approach, where freshly regenerated cellulose II films are stacked without the need for solvents (for impregnation and/or partial dissolution), chemical modifications, or resins. The structural and mechanical properties of these all-cellulose laminates were thoroughly investigated. This simple and scalable procedure results in transparent laminates with exceptional mechanical properties comparable to or even superior to common plastics, with E-modulus higher than 9 GPa for a single layer and 7 GPa for the laminates. These laminates are malleable and can be easily patterned. Depending on the number of layers, they can be thin and flexible (with just one layer) or thick and rigid (with three layers). Laminates were also doped with 10 wt% undissolved fibers without compromising their characteristics. These innovative all-cellulose laminates present a robust, eco-friendly alternative to traditional synthetic materials, thus bridging the gap between environmental responsibility and high-performance functionality.

16.
Yakugaku Zasshi ; 144(9): 905-910, 2024.
Article in Japanese | MEDLINE | ID: mdl-39218658

ABSTRACT

While decreased renal function is a known risk factor for hypermagnesemia caused by magnesium oxide (MgO), few studies have comprehensively investigated other contributing factors. In this study, the researchers analyzed the risk factors for hypermagnesemia development in 256 inpatients receiving MgO treatment at the Matsuyama Shimin Hospital. Multivariate analysis identified blood urea nitrogen ≧22 mg/dL, estimated glomerular filtration rate ≦43.1 mL/min, and MgO ≧1000 mg/d as risk factors. Additionally, the researchers' findings suggest a correlation between the number of risk factors and the incidence of hypermagnesemia, including the prevalence of Grade 3 cases. Interestingly, low body mass index emerged as a potential risk factor even in patients without the three identified factors. These findings highlight the importance for pharmacists to advocate for routine serum Mg level monitoring in patients with the risk factors identified in this study.


Subject(s)
Blood Urea Nitrogen , Body Mass Index , Magnesium Oxide , Magnesium , Magnesium Oxide/adverse effects , Magnesium Oxide/administration & dosage , Humans , Risk Factors , Magnesium/blood , Female , Male , Aged , Glomerular Filtration Rate , Middle Aged , Aged, 80 and over , Multivariate Analysis , Adult
17.
J Contam Hydrol ; 266: 104414, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39154557

ABSTRACT

Composite with a high specific surface area of 224.62 m2 g-1 was prepared by adding urea as a nitrogen source to hazelnut shell biochar (HSB). Nitrogen doping significantly enhanced the ability of biochar for Cr(VI) elimination, achieving twice the removal efficiency of unmodified biochar. The impacts of varying the pH and initial concentrations on Cr(VI) removal by urea-modified biochar (N-HSB) were investigated. The Cr(VI) removal by N-HSB was better described by intra particle diffusion model and pseudo-second order kinetic model under optimal conditions. Furthermore, XPS, FTIR, SEM, and BET analyses were used to verify the pivotal roles of oxygen- and nitrogen-containing functional groups. Electrostatic attraction, redox reaction, and complexation constituted the principal mechanisms facilitating Cr(VI) elimination by N-HSB. This study demonstrated that the modification of biochar with urea as a nitrogen source represented a promising strategy for enhancing the removal capacity of biochar for Cr(VI) in aqueous environments.


Subject(s)
Charcoal , Chromium , Corylus , Urea , Water Pollutants, Chemical , Charcoal/chemistry , Corylus/chemistry , Chromium/chemistry , Urea/chemistry , Water Pollutants, Chemical/chemistry , Adsorption , Kinetics , Water Purification/methods , Hydrogen-Ion Concentration
18.
Angew Chem Int Ed Engl ; : e202410938, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39092496

ABSTRACT

The electrocatalytic C-N coupling from CO2 and nitrate emerges as one of the solutions for waste upgrading and urea synthesis. In this work, we constructed electron-deficient Cu sites by the strong metal-polymer semiconductor interaction, to boost efficient and durable urea synthesis. In situ Raman spectroscopy identified the existence of electron-deficient Cu sites and was able to withstand electrochemical reduction conditions. Operando synchrotron-radiation Fourier transform infrared spectroscopy and theoretical calculations disclosed the vital role of electron-deficient Cu in adsorption and C-N coupling of oxygen-containing species. The electron-deficient Cu displayed a high urea yield rate of 255.0 mmol h-1 g-1 at -1.4 V versus the reversible hydrogen electrode and excellent electrochemical durability, superior than that of non-electron-deficient counterpart with conductive carbon material as the support. It can be concluded that the regulation of site electronic structure is more important than the optimization of catalyst conductive properties in the C-N coupling reactions.

19.
J Pediatr Genet ; 13(3): 205-210, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39086438

ABSTRACT

Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, an inborn error of metabolism, is an inherited syndrome caused by loss-of-function mutations in the SLC25A15, resulting in ornithine translocase1 (ORNT1) deficiency. Disrupted ornithine transportation in an affected individual usually manifests with the accumulation of intermediate metabolites, leading to neurological impairment, hepatitis, and/or protein intolerance at various ages of onset. In this paper, we report a compound heterozygous mutation in SLC25A15 from a 2-year-old girl who presented with neurological alterations and hepatic failure. Before developing neurological sequelae, she had signs of globally delayed development. The accumulation of toxic metabolites may explain these neurological consequences. After biochemical confirmation of HHH, whole-exome sequencing (WES) was performed, which identified mutations at codons 21 and 179 of SLC25A15 that are predicted to result in the loss of function of ORNT1. Each of the mutations was found to be inherited from one of her parents. After therapy, her toxic metabolites decreased significantly. In conclusion, HHH syndrome frequently manifests with nonspecific symptoms and unapparent biochemical profiles, which may lead to delayed diagnosis. Correction of the accumulating metabolites is necessary to prevent irreversible neurological impairment. Furthermore, performing a WES provides a shortcut for accurate diagnosis.

20.
Cell Biol Toxicol ; 40(1): 64, 2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39096436

ABSTRACT

BACKGROUND AND PURPOSE: Colorectal cancer (CRC) is a widespread malignancy with a complex and not entirely elucidated pathogenesis. This study aims to explore the role of Bifidobacterium in the urea cycle (UC) and its influence on the progression of CRC, a topic not extensively studied previously. EXPERIMENTAL APPROACH: Utilizing both bioinformatics and experimental methodologies, this research involved analyzing bacterial abundance in CRC patients in comparison to healthy individuals. The study particularly focused on the abundance of BA. Additionally, transcriptomic data analysis and cellular experiments were conducted to investigate the impact of Bifidobacterium on ammonia metabolism and mitochondrial function, specifically examining its regulation of the key UC gene, ALB. KEY RESULTS: The analysis revealed a significant decrease in Bifidobacterium abundance in CRC patients. Furthermore, Bifidobacterium was found to suppress ammonia metabolism and induce mitochondrial dysfunction through the regulation of the ALB gene, which is essential in the context of UC. These impacts contributed to the suppression of CRC cell proliferation, a finding corroborated by animal experimental results. CONCLUSIONS AND IMPLICATIONS: This study elucidates the molecular mechanism by which Bifidobacterium impacts CRC progression, highlighting its role in regulating key metabolic pathways. These findings provide potential targets for novel therapeutic strategies in CRC treatment, emphasizing the importance of microbiota in cancer progression.


Subject(s)
Bifidobacterium , Colorectal Neoplasms , Urea , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/microbiology , Colorectal Neoplasms/pathology , Bifidobacterium/metabolism , Humans , Urea/metabolism , Animals , Cell Proliferation , Ammonia/metabolism , Mice , Mitochondria/metabolism , Cell Line, Tumor , Male , Gastrointestinal Microbiome/physiology , Female
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