Acid Production Research Articles

Enhancing fatty acid and omega-3 production in Schizochytrium sp. using developed safe-harboring expression system

BackgroundSchizochytrium, a group of eukaryotic marine protists, is an oleaginous strain, making it a highly promising candidate for the production of lipid-derived products such as biofuels and omega-3 fatty acids. However, the insufficient advancement of genetic engineering tools has hindered further advancements. Therefore, the development and application of genetic engineering tools for lipid enhancement are crucial for industrial production.ResultsTransgene expression in Schizochytrium often encounters challenges such as instability due to positional effects. To overcome this, we developed a safe-harbor transgene expression system. Initially, the sfGFP gene was integrated randomly, and high-expressing transformants were identified using fluorescence-activated cell sorting. Notably, HRsite 2, located approximately 3.2 kb upstream of cytochrome c, demonstrated enhanced sfGFP expression and homologous recombination efficiency. We then introduced the 3-ketoacyl-ACP reductase (KR) gene at HRsite 2, resulting in improved lipid and docosahexaenoic acid (DHA) production. Transformants with KR at HRsite 2 exhibited stable growth, increased glucose utilization, and a higher lipid content compared to those with randomly integrated transgenes. Notably, these transformants showed a 25% increase in DHA content compared to the wild-type strain.ConclusionThis study successfully established a robust homologous recombination system in Schizochytrium sp. by identifying a reliable safe harbor site for gene integration. The targeted expression of the KR gene at this site not only enhanced DHA production but also maintained growth and glucose consumption rates, validating the efficacy of the safe-harbor approach. This advancement in synthetic biology and metabolic engineering paves the way for more efficient biotechnological applications in Schizochytrium sp.

Electrosynthesis of Amino Acids from Biomass and Nitrate at Industrial Current Densities Using Porous PbBi Electrodes.

Electrosynthesis is a rising and attractive method for efficient amino acid production. However, industrial-grade electrosynthesis of high-value amino acids from simple carbon and nitrogen substrates is confronted with a great challenge. Herein, we design a dual-site PbBi alloy catalyst for various amino acids' electrosynthesis from keto acids and nitrate. An alanine Faradaic efficiency of 59.7% is delivered at -1.5 V vs SCE, reaching the industrial current density of 570 mA cm-2 with high catalytic durability of the porous Pb1Bi0.1 catalyst. In the tandem reaction process, nitrate is first converted to NH2OH via electrochemical reduction mainly over the Bi site. Then the obtained NH2OH integrates with the α-keto acid to form the oxime intermediate. Lastly, the Pb site facilitates the electroreduction of oxime to the final amino acids. More importantly, over 10 kinds of α-amino acids can be successfully synthesized in excellent FE and high yield at high current density, indicating the superior catalytic activity and wide universality of our strategy. In short, this work opens up a novel approach to realize the one-pot electrosynthesis of various amino acids from renewable biomass feedstocks and nitrate waste industrially.

Lactiplantibacillus argentoratensis AGMB00912 alleviates diarrhea and promotes the growth performance of piglets during the weaning transition

BackgroundPreventing post-weaning diarrhea (PWD) in weaned piglets is a crucial challenge in the swine production industry. The stress of weaning, dietary shifts from maternal milk to solid feed, and environmental changes lead to decreased microbial diversity, increased pathogen abundance, and compromised intestinal integrity. We have previously identified Lactiplantibacillus argentoratensis AGMB00912 (LA) in healthy porcine feces, which demonstrated antimicrobial activity against pathogens and enhanced short-chain fatty acid production. This research aimed to evaluate the efficacy of LA strain supplementation as a strategy to inhibit PWD and enhance overall growth performance in weaned piglets.ResultsLA supplementation in weaned piglets significantly increased body weight gain, average daily gain, and average daily feed intake. It also alleviated diarrhea symptoms (diarrhea score and incidence). Notably, LA was found to enrich beneficial microbial populations (Lactobacillus, Anaerobutyricum, Roseburia, Lachnospiraceae, and Blautia) while reducing the abundance of harmful bacteria (Helicobacter and Campylobacter). This not only reduces the direct impact of pathogens but also improves the overall gut microbiota structure, thus enhancing the resilience of weaned piglets. LA treatment also promotes the growth of the small intestinal epithelial structure, strengthens gut barrier integrity, and increases short-chain fatty acid levels in the gut.ConclusionsThe study findings demonstrate the promising potential of LA in preventing PWD. Supplementation with the LA strain offers a promising feed additive for improving intestinal health and growth in piglets during the weaning transition, with the potential to significantly reduce the incidence and severity of PWD.

Effect of D-limonene on volatile fatty acids production from anaerobic fermentation of waste activated sludge under pH regulation: performance and mechanisms

D-limonene extracted from citrus peels possesses an inhibitory effect on methanogenic archaea. This study is aimed to bridge the research gap on the influence of D-limonene on volatile fatty acids (VFA) production from waste activated sludge (WAS) and to address the low VFA yield in standalone anaerobic fermentation of WAS. When the initial pH was not controlled, 1.00 g/g TSS D-limonene resulted in a VFA accumulation of 1175.45 ± 101.36 mg/L (174.45 ± 8.13 mgCOD/gVS). When the initial pH was controlled at 10 and the D-limonene concentration was 0.50 g/g TSS, the VFA accumulation reached 2707.44 ± 183.65 mg/L (445.51 ± 17.10 mgCOD/gVS). The pH-regulated D-limonene treatment enhanced solubilization and acidification, slightly inhibited hydrolysis, and significantly suppressed methanogenesis. D-limonene under alkaline conditions can increase the relative abundance of Clostridium_sensu_stricto, significantly enhancing acidification. Moreover, it markedly inhibited methanogenesis by particularly reducing the relative abundance of Methanothrix that was responsible for acetate consumption, thus favoring the accumulation of VFA. The research reveals the potential mechanism of pH regulation and D-limonene on anaerobic fermentation acid production, providing a theoretical basis for improving the acid production performance of the anaerobic fermentation of WAS.

Investigation on the influence of GPI-AP for the production of malic acid in Aspergillus niger

Based on the potential of microbial fermentation in the sustainable and environmentally friendly production of L-malic acid (L-MA), this study aims to investigate the effect of glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) on enhancing the stability of Aspergillus niger (A. niger) cell wall to increase L-MA production. Through experiments, we discovered and screened GPI2, a GPI-anchored cell surface glycoprotein, and confirmed for the first time that it has a promoting effect on L-MA, a metabolite of A. niger. This recombinant strain RG0098 that overexpressed gpi2 showed an increase in cell wall thickness and robustness, a decrease in intracellular reactive oxygen species (ROS) levels, which improved the antioxidant capacity. After 108 h of fermentation, the production of L-MA reached 114.7 ± 2.12 g/L, and the productivity was 1.06 ± 0.025 g/L/h. The strain RG0098 has enhanced the productivity of L-MA by a notable margin of 49.7 %. This study provides a sustainable and environmentally friendly pathway for the production of L-MA through microbial fermentation.

Biosynthesis of plant-derived triterpenoid asiatic acid in Saccharomyces cerevisiae cell factories

Asiatic acid, a bioactive component of Centella asiatica (L.) Urban, exhibits plentiful valuable pharmacological properties. Herein, we engineered Saccharomyces cerevisiae to produce asiatic acid. Initially, asiatic acid was synthesized by expressing the Centella asiatica cytochrome P450 monooxygenases CYP714E19 and CYP716C11 in a Saccharomyces cerevisiae strain optimized for ursolic acid production. The engineered strain yielded 0.42 ± 0.01 mg/L and 0.067 ± 0.0013 mg/g dry cell weight (DCW) of asiatic acid. Subsequently, a suitable cytochrome P450 reductase was screened, and key enzymes were overexpressed to effectively convert ursolic acid to asiatic acid. Strengthening heme biosynthesis, promoting endoplasmic reticulum (ER) expansion, and enhancing the cofactor supply were implemented to improve P450 catalytic activity. Additionally, a PDZ-PDZlig-mediated protein self-assembly strategy was used to improve the efficiency of the CYP714E19 and CYP716C11 catalytic cascade. Finally, the highest production was achieved (30.09 ± 0.15 mg/L, 4.09 ± 0.01 mg/g DCW) in microbial cell factories. This work establishes a foundation for efficient production of asiatic acid.

Rational Design of Formate Dehydrogenase for Enhanced Thermal Stability and Catalytic Activity in Bioelectrocatalysis.

Formate dehydrogenase can be utilized as a biocatalyst in the bioelectrocatalysis of converting CO2 into formic acid. However, its industrial application has been hindered by limited thermal stability. This study successfully obtained a mutant (D533S/E684I) with enhanced thermal stability and catalytic activity through the rational design of flexible regions. The mutant exhibited a half-life (t1/2) 1.5 times longer than the wild type (WT) at 35 °C, along with a specific enzyme activity 7.46 times higher than that of the WT. Additionally, the catalytic efficiency (kcat/Km value) of the mutant toward the substrate was 2.72 s-1·mM-1, representing a 19.4-fold increase compared to the WT (0.14 s-1·mM-1). Formic acid production reached 53.4 mM through bioelectrocatalysis after 10 h, utilizing the mutant as the biocatalyst. Molecular dynamics simulations and structural analysis were employed to investigate the molecular mechanisms behind the enhanced thermal stability and activity. The displacement of a highly flexible region in the mutant may counteract the stability-activity trade-off. This study proposed a method for improving both thermal stability and activity in enzyme evolution.

Application of propionate-producing bacterial consortium in ruminal methanogenesis inhibited environment with bromoethanesulfonate as a methanogen direct inhibitor.

Methane production in ruminants is primarily due to the conversion of metabolic hydrogen (H2), produced during anaerobic microbial fermentation, into methane by ruminal methanogens. While this process plays a crucial role in efficiently disposes of H2, it also contributes to environmental pollution and eliminating methane production in the rumen has proven to be challenging. This study investigates the use of probiotics, specifically propionate-producing bacteria, to redirect accumulated H2 in a methane-mitigated environment. For this objective, we supplemented experimental groups with Lactiplantibacillus plantarum and Megasphaera elsdenii for the reinforced acrylate pathway (RA) and Selenomonas ruminantium and Acidipropionibacterium thoenii for the reinforced succinate pathway (RS), as well as a consortium of all four strains (CB), with the total microbial concentration at 1.0 × 1010 cells/mL. To create a methane-mitigated environment, 2-bromoethanesulfonate (BES) was added to all experimental groups at a dose of 15 mg/0.5 g of feed. BES reduced methane production by 85% in vitro, and the addition of propionate-producing bacteria with BES further decreased methane emission by up to 94% compared with the control (CON) group. Although BES did not affect the alpha diversity of the ruminal bacteriome, it reduced total volatile fatty acid production and altered beta diversity of ruminal bacteriota, indicating microbial metabolic adaptations to H2 accumulation. Despite using different bacterial strains targeting divergent metabolic pathways (RA and RS), a decrease in the dominance of the [Eubacterium] ruminantium group suggesting that both approaches may have a similar modulatory effect. An increase in the relative abundance of Succiniclasticum in the CB group suggests that propionate metabolism is enhanced by the addition of a propionate-producing bacterial consortium. These findings recommend using a consortium of propionate-producing bacteria to manage H2 accumulation by altering the rumen bacteriome, thus mitigating the negative effects of methane reduction strategies.

Caproiciproducens converts lactic acid into caproic acid during Chinese strong-flavor Baijiu brewing

Strong-flavor Baijiu, a type of Chinese liquor, is produced through anaerobic solid-state fermentation in a sealed mud pit. Ethyl caproate, the characteristic flavor compound of strong-flavor Baijiu, is influenced by caproic acid-producing bacteria in the pit mud. To better understand the formation of caproic acid, this study investigated the microbial composition and physicochemical parameters of pit mud from different layers (top, middle, and bottom) in Hubei and Sichuan provinces, China. The results revealed that Caproiciproducens plays a key role in caproic acid production by using lactic acid as a substrate, with its abundance increasing with the depth of the pit mud. A strain Caproiciproducens sp. R1, isolated from the pit mud, was shown to produce caproic acid from lactic acid within an initial pH range of 5.5–9.0 and lactic acid concentrations of 1 %–5 % (m/v). In addition, inoculation of strain R1 into Huangshui (a lactic acid-rich liquid from Baijiu production) resulted in 40.72 mM caproic acid production. This study demonstrates that Caproiciproducens plays a crucial role in caproic acid production from lactic acid during the fermentation process of strong-flavor Baijiu.

Isolation and characterization of plant growth-promoting rhizobacteria (PGPR) from eelgrass Zostera marina rhizosphere: implications for bioremediation

Plant growth-promoting rhizobacteria (PGPR) play a crucial role in enhancing plant growth. However, investigations into the presence and function of PGPR in seagrass rhizospheres remain relatively limited. In this study, we isolated 45 strains of PGPR from Zostera marina rhizospheres and assessed their functional attributes. Additionally, we evaluated the performance of these candidate strains under varying environmental conditions, such as temperature, salinity, and pH. Out of the 45 analyzed strains, 6 were found to possess the nifH gene; some strains also exhibited the ability to solubilize inorganic phosphorus, with dissolved phosphorus content ranging widely from 14.6 to 393.9 mg l-1. Eleven strains demonstrated indole-3-acetic acid production, with yields spanning from 16.3 to 42.8 mg l-1. Siderophores and ammoniated proteins were produced by 32 and 20 strains, respectively. Notably, 5 PGPR strains (F65, G84, G85, G86, and I109) displayed multiple growth-promoting properties along with strong adaptability to a wide range of physicochemical conditions. This study highlights the potential reservoir of PGPR in the eelgrass rhizosphere and provides significant implications for utilizing these bacteria to enhance the success rate of restoring degraded seagrass meadows.

Development of an infant colon simulating in vitro model, I-TIM-2, to study the effects of modulation strategies on the infant gut microbiome composition and function.

The early life stages are critical for the development of the gut microbiome. Variables such as antibiotics exposure, birth-mode via Cesarean section, and formula feeding are associated with disruptions in microbiome development and are related to adverse health effects later in life. Studying the effects of microbiome-modulating strategies in infants is challenged by appropriate ethical constraints. Therefore, we developed I-TIM-2, an infant in vitro colonic model based on the validated, computer-controlled, dynamic model of the colon, TIM-2. The system, consisting of four separate compartments, was inoculated with feces from four healthy, primarily breastfed infants, displaying distinctive microbiome profiles. For each infant's fecal sample, a 96-h experiment was performed, with two compartments receiving an infant diet adapted medium and two compartments additionally receiving five human milk oligosaccharides (HMOs) in physiological concentrations and proportions. Bacterial composition was determined by shotgun metagenomics and qPCR. Concentrations of short-chain fatty acids (SCFAs) and HMOs were determined by LC-MS. Microbial diversity and high amounts of inoculum-derived species were preserved in the model throughout each experiment. Microbiome composition and SCFA concentrations were consistent with published data from infants. HMOs strongly modulated the microbiome composition by stimulating relative proportions of Bifidobacterium. This affected the metabolic output and resulted in an increased production of acetic and formic acid, characteristic of bifidobacterial HMO metabolism. In conclusion, these data demonstrate the development of a valid model to study the dynamics and modulations of the infant gut microbiome and metabolome.IMPORTANCEThe infant gut microbiome is intricately linked to the health of its host. This is partly mediated through the bacterial production of metabolites that interact with the host cells. Human milk shapes the establishment of the infant gut microbiome as it contains human milk sugars that select for primarily bifidobacteria. The establishment can be disrupted by modern interventions such as formula feeding. This can alter the microbiome composition and metabolite production profile, which can affect the host. In this article, we set up an infant in vitro colonic model to study microbiome interactions and functions. In this model, we investigated the effects of human milk sugars and their promotion of bifidobacteria at the expense of other bacteria. The model is an ideal system to assess the effects of various modulating strategies on the infant gut microbiome and its interactions with its host.

Natural variation in MdNAC5 contributes to fruit firmness and ripening divergence in apple

Abstract Fruit firmness is an important trait for characterizing the quality and value of apple. It is also serves as an indicator of fruit maturity, as it is a complex trait regulated by multiple genes. Re-sequencing techniques can be employed to elucidate variations in such complex fruit traits. Here, the whole genomes of 294 F1 hybrids of ‘Fuji’ and ‘Cripp's Pink’ were re-sequenced, and a high-density bin-map was constructed using 5,014 bin markers with a total map distance of 2,213.23 cM and an average map distance of 0.44 cM. Quantitative trait loci (QTLs) of traits related to fruit were mapped, and an A-T allele variant identified in the coding region of MdNAC5 was found to potentially regulate fruit firmness and ripening. The overexpression of MdNAC5A resulted in higher production of methionine and 1-aminocyclopropanecarboxylic acid compared to MdNAC5T, leading to reduced fruit firmness and accelerated ripening in apples and tomatoes. Furthermore, the activities of MdNAC5A and MdNAC5T were enhanced through their differential binding to the promoter regions of MdACS1 and MdERF3. Spatial variations in MdNAC5A and MdNAC5T caused changes in MdACS1 expression following their interaction with MdERF3. Ultimately, utilizing different MdNAC5 alleles offers a strategy to manipulate fruit firmness in apple breeding.

Increasing degree of substitution inhibits acetate while promotes butyrate production during in vitro fermentation of citric acid-modified rice starch

Citric acid-modified starch functions as a resistant starch, while the combined effects of its fine molecular structure and degree of substitution on gut microbiota are not well understood. To this end, citric acid-modified starches with varying degrees of substitution were synthesized from rice starches with distinct molecular structures and their impact on gut microbiota composition and short-chain fatty acid (SCFA) production was analyzed. Notably, rice starch with a higher degree of substitution significantly reduced acetate production, while promoted butyrate production. Correlation analysis further suggested that amylopectin chains with 12 < DP ≤ 36 and amylose chains with 100 < DP ≤ 500 alter the growth of Faecalibacterium_prausnitzii and Bacteroides_vulgatus, consequentially determining the production of SCFAs. Collectively, these findings indicate that citric acid-modified rice starch with different degrees of substitution can target specific gut bacteria and SCFA production, thus conferring beneficial impact on human health.

Serum metabonomics reveal the effectiveness of human placental mesenchymal stem cell therapy for primary sclerosing cholangitis.

The metabolic patterns of human placental-derived mesenchymal stem cell (hP-MSC) treatment for primary sclerosing cholangitis (PSC) remain unclear, and therapeutic effects significantly vary due to individual differences. Therefore, it is crucial to investigate the serological response to hP-MSC transplantation through small molecular metabolites and identify easily detectable markers for efficacy evaluation. Using Mdr2-/- mice as a PSC model and Mdr2+/+ mice as controls, the efficacy of hP-MSC treatment was assessed based on liver pathology, liver enzymes, and inflammatory factors. Serum samples were collected for 12C-/13C-dansylation and DmPA labeling LC-MS analysis to investigate changes in metabolic pathways after hP-MSC treatment. Key metabolites and regulatory enzymes were validated by qRT-PCR and Western blotting. Potential biomarkers of hP-MSC efficacy were identified through correlation analysis and machine learning. Collectively, the results of the liver histology, serum liver enzyme levels, and inflammatory factors supported the therapeutic efficacy of hP-MSC treatment. Based on significant differences, 41 differentially expressed metabolites were initially identified; these were enriched in bile acid, lipid, and hydroxyproline metabolism. After treatment, bile acid transport was accelerated, whereas bile acid production was reduced; unsaturated fatty acid synthesis was upregulated overall, with increased FADS2 and elongase expression and enhanced fatty acid β-oxidation; hepatic proline 4-hydroxylase expression was decreased, leading to reduced hydroxyproline production. Correlation analysis of liver enzymes and metabolites, combined with time trends, identified eight potential biomarkers: 2-aminomuconate semialdehyde, L-1-pyrroline-3-hydroxy-5-carboxylic acid, L-isoglutamine, and maleamic acid were more abundant in model mice but decreased after hP-MSC treatment. Conversely, 15-methylpalmitic, eicosenoic, nonadecanoic, and octadecanoic acids were less abundant in model mice but increased after hP-MSC treatment. This study revealed metabolic regulatory changes in PSC model mice after hP-MSC treatment and identified eight promising biomarkers, providing preclinical evidence to support therapeutic applications of hP-MSC.

Transcriptomics identify the triggering of citrate export as the key event caused by manganese deficiency in Aspergillus niger.

Citric acid is produced on industrial scale by batch fermentation of the filamentous fungus Aspergillus niger. High-yield citric acid production requires a low (<5 ppb) manganese(II) ion concentration in the culture broth. However, the requirement for this deficiency has not been investigated on a functional genomics level. Here, we compared the transcriptome of a citric acid hyper-producer A. niger strain grown under citric acid-producing conditions in 6-L scale bioreactors at Mn2+ ion-deficient (5 ppb) and Mn2+ ion-sufficient (100 ppb) conditions at three early time points of cultivation. We observed that Mn2+ deficiency triggers an upregulation of the citrate exporter gene cexA and provides functional evidence that this event is responsible for citrate overflow. In addition to the industrial relevance, this is the first study that examined the role of Mn2+ ion deficiency in a heterotrophic eukaryotic cell on a genome-wide scale.

Examining the complex Interplay between gut microbiota abundance and short-chain fatty acid production in amyotrophic lateral sclerosis patients shortly after onset of disease.

This study aimed to assess differences in the enteral microbiome of relatively recent-onset amyotrophic lateral sclerosis (ALS) patients (< 6-15 months since symptom onset) compared to healthy individuals, focusing on short-chain fatty acids (SCFAs) as potential mediators of host metabolism. We included 28 volunteers (16 ALS, 12 controls) with informed consent. No significant effect of ALS on alpha diversity (measuring the variety and abundance of species within a single sample, and indicating the health and complexity of the microbiome) was observed, but ALS patients had higher abundances of Fusobacteria and Acidobacteria. ALS subtypes influenced specific species, with increased Fusobacteria and Tenericutes in spinal ALS compared to bulbar ALS. ALS patients showed increased Enterobacter, Clostridium, Veillonella, Dialister, Turicibacter, and Acidaminococcus species and decreased Prevotella, Lactobacillus, and Butyricimonas. Correlations between species varied between ALS patients and healthy individuals and among ALS subtypes. No significant differences in SCFA concentrations were found, but spinal ALS samples showed a trend towards decreased propionate content. Relationships between SCFAs and phyla colonization differed by disease status. This study suggests distinct enteral microbiome characteristics in ALS patients, though the implications are unclear. Further research is needed to determine if these differences are causative or consequential and to explore their potential as diagnostic or therapeutic targets. The study also underscores the heterogeneity of microbiome constraints in ALS and the need for more research into ALS and SCFA metabolism.

GAS5 promotes glucose metabolism reprogramming and resistance to ferroptosis of endothelial progenitor cells through the miR-495-3p/SIX1 and IGF2BP2/NRF2 dual-regulatory pathways in coronary heart disease.

We aimed to explore the potential along with mechanism of lncRNA growth arrest-specific 5 (GAS5) in modulating glucose metabolism and ferroptosis of endothelial progenitor cells (EPCs) in coronary heart disease (CHD). CCK-8, flow cytometry, EdU, colony formation, scratch test as well as transwell assays were implemented to assess cell biological behaviors. Glucose uptake testing, lactic acid production assay, and detection of extracellular acidification rate (EACR) together with oxygen consumption rate (OCR) were used to assess glucose metabolism. Iron, GSH and MDA detection were used to measure ferroptosis. Besides, a series of mechanical experiments were implemented to clarify the modulatory relationship between GAS5 and nuclear factor erythroid 2-related factor 2 (NRF2) as well as sine oculis homeobox 1 (SIX1). We found that GAS5 was down-regulated in CHD patients relative to healthy controls. GAS5 depletion repressed EPCs proliferation, migration along with invasion while elevated cell apoptosis. GAS5 promoted the reprogramming of glucose metabolism and inhibited ferroptosis in EPCs. GAS5 affected glycometabolic reprogramming and ferroptosis resistance through regulating SIX1 and NRF2. On the one hand, GAS5 promoted NRF2 mRNA stability through IGF2BP2. On the other hand, GAS5 regulated the miR-495-3p/SIX1 axis in EPCs. To sum up, GAS5 promotes glucose metabolism reprogramming and resistance to ferroptosis of EPCs through the miR-495-3p/SIX1 and IGF2BP2/NRF2 dual-regulatory pathways in CHD.

Evolution of the doctrine of Zollinger-Ellison syndrome. Literature review

Zollinger–Ellison syndrome (ZES) is a rare pathology that does not have specific clinical manifestations and is not always diagnosed in time. This is attributed to doctors’ insufficient awareness of this pathology and the limited availability of the necessary examination methods. Foreign literary sources on this problem are analysed. Historical data regarding the discovery of this pathology and the origin of the syndrome’s name are provided. The epidemiology of the disease is highlighted. The most characteristic clinical manifestations and possible complications of ZES are described in detail. The characteristic changes in gastric acid production associated with this pathology and their diagnostic value (sensitivity and specificity) are presented. At the same time, indicators of both basal and maximal stimulated gastric acid production are significantly increased. The most important stage in the examination of patients with suspected ZES is the determination of blood gastrin levels. At the same time, it is shown that it is not always possible to make definitive judgements in support of ZES based on gastrin indicators. An absolute criterion in favor of ZES is fasting gastrin values of 1000 pg/ml or more. When gastrin levels are less than this indicator, tests using secretin or calcium gluconate have significant diagnostic value. In these circumstances, tests with secretin or calcium gluconate are mandatory. The information on the possible localization of gastrin, the incidence of malignant transformation, and the mechanism of metastasis is given. Methods of determining gastrin localization, sensitivity, and specificity are described in detail. Based on the findings, a differentiated treatment strategy for patients with ZES is provided. Indications and contraindications for surgical and medical treatment of patients with ZES are given. The prospects of a new treatment direction ‑ the use of targeted radiotherapy ‑ are shown. These patients require constant monitoring by a gastroenterologist and a surgeon and periodically undergo the necessary examinations.

A rare occurrence of xanthine urolithiasis in siblings with Lesch–Nyhan syndrome treated with Allopurinol—a case report

Abstract Introduction Lesch–Nyhan syndrome (LNS) is an X-linked disorder affecting the metabolism of the purine salvage pathway leading to excessive serum uric acid production. Treatment of hyperuricemia with Allopurinol is usually effective to lower serum uric acid concentration to acceptable levels. Allopurinol blocks the conversion of hypoxanthine and xanthine to serum uric acid in the purine degradation pathway. The effect of Allopurinol may result in excessive buildup of xanthine, potentially resulting in urolithiasis composed of xanthine. This rare occurrence poses a unique challenge maintaining a balance between lowering hyperuricemia and preventing the development of xanthine urolithiasis. This case report includes two siblings with LNS treated with Allopurinol who developed xanthine urolithiasis. Case description Patients are siblings, a 22-year-old male and a 21-year-old female, with LNS diagnosed in early childhood. They both share similar manifestations of the disease and were treated with Allopurinol with an intended therapeutic window of serum uric acid levels since diagnosis. Both were prone to developing urolithiasis and nephrolithiasis, the male more than the female, regardless of the medical regimen. Uric acid and calcium levels were normal in the serum and urine. Chemical analysis of calculi eliminated by both siblings revealed xanthine stones. Conclusions Patients with LNS tend to develop stones composed of urate. Rarely, they can also precipitate stones composed of xanthine resulting from its buildup in serum and urine by Allopurinol. This complication should be considered in all patients undergoing treatment with Allopurinol. Careful clinical monitoring and dose adjustments of Allopurinol must balance the need to control hyperuricemia with avoiding excessive blockade of hypoxanthine.

Conversion of Cellobiose to Formic Acid as a Biomass-Derived Renewable Hydrogen Source Using Solid Base Catalysts.

Formic acid is considered a promising hydrogen carrier. Biomass-derived formic acid can be obtained by oxidative decomposition of sugars. This study explored the production of formic acid from cellobiose, a disaccharide consisting of d-glucose linked by β-glycosidic bonds using heterogeneous catalysts under mild reaction conditions. The use of alkaline earth metal oxide solid base catalysts like CaO and MgO in the presence of hydrogen peroxide could afford formic acid from cellobiose at 343 K. While CaO gave 14 % yield of formic acid, the oxide itself was converted to a harmful metal peroxide, CaO2 after the reaction. In contrast, MgO could produce formic acid without the formation of the metal peroxide. The difficulty in selectively synthesizing formic acid from cellobiose using these solid base catalysts was due to the poor conversion of cellobiose to glucose. Using a combination of solid acid and base catalysts, a high formic acid yield of 33 % was obtained under mild reaction conditions due to the quantitative hydrolysis of cellobiose to glucose by a solid acid followed by the selective decomposition of glucose to formic acid by a solid base.