Search

To date, the changes in maternal metabolic response associated with prenatal aflatoxin exposure remain largely unknown. This study investigated the effects of prenatal aflatoxin exposure on the maternal serum metabolome in rural Ethiopia. A total of 309 pregnant women were enrolled prospectively, and their serum aflatoxin concentrations were measured using targeted liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS). Serum metabolic fingerprints were obtained using laser-assisted rapid evaporative ionization mass spectrometry (LA-REIMS), followed by combination of univariate and multivariate statistical modelling to evaluate changes in circulating metabolic features between aflatoxin-exposed and unexposed mothers and to select discriminatory metabolic features. The analysis revealed that 81.8% of women were exposed to aflatoxins, with a median concentration of 12.9 pg/mg albumin. The orthogonal partial least square discriminant analysis (OPLS-DA) regression model demonstrated significant disparities in the serum metabolome when comparing Ethiopian pregnant women with low vs high aflatoxin exposure. Thirty-two differentially expressed metabolic features were identified, affecting aminoacyl-tRNA biosynthesis pathway. Several discriminatory metabolites have been identified, including glutamine, tryptophan, tyrosine, carnosine, and 1-methylnicotinamide. In conclusion, our findings indicate that aflatoxin exposure during pregnancy have shown disparities in the maternal serum metabolome, primarily affecting protein synthesis. Further research is needed to identify specific metabolite biomarkers and elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Bariatric surgery is an effective treatment for morbid obesity. However, a subset of individuals seeking bariatric surgery may exhibit a metabolically healthy obesity (MHO) phenotype, suggesting that they may not experience metabolic complications despite being overweight. Objective: This study aimed to determine the prevalence and metabolic features of MHO in a population undergoing bariatric surgery. Methods: A representative sample of 665 participants aged 14 or older who underwent bariatric surgery at our center from January 1, 2010 to January 1, 2020 was included in this cohort study. MHO was defined based on specific criteria, including blood pressure, waist-to-hip ratio, and absence of diabetes. Results: Among the 665 participants, 80 individuals (12.0%) met the criteria for MHO. Female gender (P =.021) and younger age (P <.001) were associated with a higher likelihood of MHO. Smaller weight and BMI were observed in individuals with MHO. However, a considerable proportion of those with MHO exhibited other metabolic abnormalities, such as fatty liver (68.6%), hyperuricemia (55.3%), elevated lipid levels (58.7%), and abnormal lipoprotein levels (88%). Conclusion: Approximately 1 in 8 individuals referred for bariatric surgery displayed the phenotype of MHO. Despite being metabolically healthy based on certain criteria, a significant proportion of individuals with MHO still exhibited metabolic abnormalities, such as fatty liver, hyperuricemia, elevated lipid levels, and abnormal lipoprotein levels, highlighting the importance of thorough metabolic evaluation in this population. [ABSTRACT FROM AUTHOR]

Fermentative features of doenjang-meju, a traditional Korean soybean brick, were investigated over 45 days via genome-centered metatranscriptomics. The pH value rapidly decreased within 10 days and successively increased after 20 days, along with an initial bacterial growth, including lactic acid bacteria, and subsequent fungal growth, suggesting their association. Polysaccharides and lipids underwent degradation, and amino acids, free sugars, and organic acids increased during the early stage. Metagenome analysis identified Aspergillus, Bacillus, Enterococcus, Staphylococcus, and Leuconostoc as major microbes, which were isolated and genome-sequenced. Metatranscriptomic analysis revealed the major roles of Bacillus and Enterococcus during the early period, shifting to Aspergillus dominance after 10 days. Metabolic pathway reconstruction and transcriptional analysis reveal that Aspergillus primarily decomposed polysaccharides to free sugars; Aspergillus and Bacillus metabolized lipids, free sugars, and organic acids generated by Enterococcus; and Aspergillus and Bacillus were instrumental in amino acid metabolism: their contributions varied by compounds and pathways.

Klebsiella aerogenes is an important opportunistic pathogen with the potential to develop resistance against last-line antibiotics, such as carbapenems, limiting the treatment options. Here, we investigated the antibiotic resistance profiles of 10 K. aerogenes strains isolated from patient samples in the intensive-care unit of a Brazilian tertiary hospital using conventional PCR and a comprehensive genomic characterization of a specific K. aerogenes strain (CRK317) carrying both the blaKPC-2 and blaNDM-1 genes simultaneously. All isolates were completely resistant to β-lactam antibiotics, including ertapenem, imipenem, and meropenem with differencing levels of resistance to aminoglycosides, quinolones, and tigecycline also observed. Half of the strains studied were classified as multidrug-resistant. The carbapenemase-producing isolates carried many genes of interest including: β-lactams (blaNDM-1, blaKPC-2, blaTEM-1, blaCTX-M-1 group, blaOXA-1 group and blaSHVvariants in 20-80% of the strains), aminoglycoside resistance genes [aac(6')-Ib and aph(3')-VI, 70 and 80%], a fluoroquinolone resistance gene (qnrS, 80%), a sulfonamide resistance gene (sul-2, 80%) and a multidrug efflux system transporter (mdtK, 70%) while all strains carried the efflux pumps Acr (subunit A) and tolC. Moreover, we performed a comprehensive genomic characterization of a specific K. aerogenes strain (CRK317) carrying both the blaKPC-2 and blaNDM-1 genes simultaneously. The draft genome assembly of the CRK317 had a total length of 5,462,831 bp and a GC content of 54.8%. The chromosome was found to contain many essential genes. In silico analysis identified many genes associated with resistance phenotypes, including β-lactamases (blaOXA-9, blaTEM-1, blaNDM-1, blaCTX-M-15, blaAmpC-1, blaAmpC-2), the bleomycin resistance gene (bleMBL), an erythromycin resistance methylase (ermC), aminoglycoside-modifying enzymes [aac(6')-Ib, aadA/ant(3")-Ia, aph(3')-VI], a sulfonamide resistance enzyme (sul-2), a chloramphenicol acetyltransferase (catA-like), a plasmidmediated quinolone resistance protein (qnrS1), a glutathione transferase (fosA), PEtN transferases (eptA, eptB) and a glycosyltransferase (arnT). We also detected 22 genomic islands, eight families of insertion sequences, two putative integrative and conjugative elements with a type IV secretion system, and eight prophage regions. This suggests the significant involvement of these genetic structures in the dissemination of antibiotic resistance. The results of our study show that the emergence of carbapenemase-producing K. aerogenes, coharboring blaKPC-2 and blaNDM-1, is a worrying phenomenon which highlights the importance of developing strategies to detect, prevent, and control the spread of these microorganisms. [ABSTRACT FROM AUTHOR]

Abstract Background Polycystic ovary syndrome (PCOS) is known as the most common endocrine/metabolic disorder in women of reproductive age. Long non-coding RNAs (lncRNAs) regulate a wide range of physiological and pathological processes. We designed this study to evaluate lncRNA H19 relative expression in patients with PCOS and to evaluate its impact on metabolic features and reproductive phenotypes of Egyptian women with polycystic ovaries. Material and methods The case–control study enrolled 50 control groups and 50 patients, with PCOS. The selection of patients with PCOS depended on the diagnosis according to the Rotterdam Consensus (2004). The lncRNA H19 were measured by real-time quantitative polymerase chain reaction (RT-qPCR). Results The lncRNA H19 level was significantly higher in the PCOS group (1.71 ± 0.48) compared to controls (0.924 ± 0.081). Furthermore, lncRNA H19 levels were significantly positively correlated with anthropometric and metabolic parameters including BMI, waist/hip ratio, TC, TG, LDL, FPG, FSI, HbA1c, and HOMA-IR. Regarding reproductive phenotypes features, hirsutism score, and AFC levels were significantly positively correlated with lncRNA H19 levels. The linear regression test revealed that BMI and AFC were the only parameters independently associated with lncRNA H19 among other studied parameters. Interestingly, receiver operating characteristic curve (ROC) analysis detected that the area under the curve (AUC) for the lncRNA H19 was 0.925 (95% CI = 0.856–0.955) with sensitivity = 96.4%, specificity = 96%, and the cutoff values (1.08). Thus, the predictive power of lncRNA H19 of PCOS was highly sensitive and specific. Conclusion PCOS patients had significantly higher lncRNA H19 levels than controls. lncRNA H19 levels were significantly positively correlated with metabolic risk factors as well as clinical and laboratory features of PCOS.

Klebsiella aerogenes is an important opportunistic pathogen with the potential to develop resistance against last-line antibiotics, such as carbapenems, limiting the treatment options. Here, we investigated the antibiotic resistance profiles of 10 K. aerogenes strains isolated from patient samples in the intensive-care unit of a Brazilian tertiary hospital using conventional PCR and a comprehensive genomic characterization of a specific K. aerogenes strain (CRK317) carrying both the blaKPC-2 and blaNDM-1 genes simultaneously. All isolates were completely resistant to β-lactam antibiotics, including ertapenem, imipenem, and meropenem with differencing levels of resistance to aminoglycosides, quinolones, and tigecycline also observed. Half of the strains studied were classified as multidrug-resistant. The carbapenemase-producing isolates carried many genes of interest including: β-lactams (blaNDM-1, blaKPC-2, blaTEM-1, blaCTX-M-1 group, blaOXA-1 group and blaSHVvariants in 20-80% of the strains), aminoglycoside resistance genes [aac(6’)-Ib and aph(3’)-VI, 70 and 80%], a fluoroquinolone resistance gene (qnrS, 80%), a sulfonamide resistance gene (sul-2, 80%) and a multidrug efflux system transporter (mdtK, 70%) while all strains carried the efflux pumps Acr (subunit A) and tolC. Moreover, we performed a comprehensive genomic characterization of a specific K. aerogenes strain (CRK317) carrying both the blaKPC-2 and blaNDM-1 genes simultaneously. The draft genome assembly of the CRK317 had a total length of 5,462,831 bp and a GC content of 54.8%. The chromosome was found to contain many essential genes. In silico analysis identified many genes associated with resistance phenotypes, including β-lactamases (blaOXA-9, blaTEM-1, blaNDM-1, blaCTX-M-15, blaAmpC-1, blaAmpC-2), the bleomycin resistance gene (bleMBL), an erythromycin resistance methylase (ermC), aminoglycoside-modifying enzymes [aac(6’)-Ib, aadA/ant(3”)-Ia, aph(3’)-VI], a sulfonamide resistance enzyme (sul-2), a chloramphenicol acetyltransferase (catA-like), a plasmid-mediated quinolone resistance protein (qnrS1), a glutathione transferase (fosA), PEtN transferases (eptA, eptB) and a glycosyltransferase (arnT). We also detected 22 genomic islands, eight families of insertion sequences, two putative integrative and conjugative elements with a type IV secretion system, and eight prophage regions. This suggests the significant involvement of these genetic structures in the dissemination of antibiotic resistance. The results of our study show that the emergence of carbapenemase-producing K. aerogenes, co-harboring blaKPC-2 and blaNDM-1, is a worrying phenomenon which highlights the importance of developing strategies to detect, prevent, and control the spread of these microorganisms.

Background: Thyroid eye disease (TED) is the most frequent orbital disease in adults and is characterized by the accumulation of orbital adipose tissue (OAT). It can lead to eyelid retraction or even vision loss. Orbital decompression surgery serves as the primary treatment for inactive TED by removing the excess OAT. However, there is a lack of alternative treatments to surgery due to the unclear understanding of the pathogenesis, particularly the metabolic features. Accordingly, our study was implemented to explore the content and features of metabolites of OATs from TED patients. Method: The OATs used in the current study were obtained from the orbital decompression surgery of seven patients with inactive TED. We also collected control OATs from eye surgical samples of five individuals with no history of autoimmune thyroid diseases, TED, or under non-inflammatory conditions. The liquid chromatography mass spectrometer was used for the measurements of the targeted metabolites. Afterwards, we performed differential metabolite assay analysis and related pathway enrichment analysis. Results: In our study, a total of 149 metabolite profiles were detected in all participants. There were significant differences in several metabolite profiles between the TED group and the control group, mainly including uric acid, oxidized glutathione, taurine, dGMP, oxidized glutathione 2, uracil, hexosephosphate, 1-methylnicotinamide, D-sedoheptulose 1,7-bisphosphate, and uridine 5'-monophosphate (all p-value < 0.05). The TED-related pathways identified included purine metabolism, beta-alanine metabolism, glutathione metabolism (p-values < 0.05). Our study found overlaps and differences including uric acid and uracil, which are in accordance with metabolites found in blood of patients with TED from previous study and several newly discovered metabolite by our study such as hexose-phosphate, 1-methylnicotinamide, Dsedoheptulose 1,7-bisphosphate, compared to those tested from blood, OAT, or urine samples reported in previous studies. Conclusion: The findings of our study shed light on the metabolic features of OAT in individuals with TED. These results may help identify new treatment targets for TED, providing potential avenues for developing alternative treatments beyond ophthalmic surgery. [ABSTRACT FROM AUTHOR]

Introduction: Dairy cattle are a vitally important ruminant in meeting the demands for high-quality animal protein production worldwide. The complicated biological process of converting human indigestible biomass into highly digestible and nutritious milk is orchestrated by various tissues. However, poorly understanding of the cellular composition and function of the key metabolic tissues hinders the improvement of health and performance of domestic ruminants. Objectives: The cellular heterogeneity, metabolic features, interactions across ten tissue types of lactating dairy cattle were studied at single-cell resolution in the current study. Methods: Unbiased single-cell RNA-sequencing and analysis were performed on the rumen, reticulum, omasum, abomasum, ileum, rectum, liver, salivary gland, mammary gland, and peripheral blood of lactating dairy cattle. Immunofluorescences and fluorescence in situ hybridization were performed to verify cell identity. Results: In this study, we constructed a single-cell landscape covering 88,013 high-quality (500

Gallium (Ga) is considered a high-tech Critical Metal, used in the manufacture of several microelectronic components containing either gallium arsenide (GaAs) or gallium nitride (GaN). The current high demand for this critical metal urges the development of effective recovery processes from secondary resources such as mine tailings or electronic recycling material. The importance of bioleaching as a biotechnological process to recover metals prompted this study, where an integrative approach combining experimental and genomic analysis was undertaken to identify potential mechanisms involved in bioleaching ability and strategies to cope with high metal(loid)s concentrations in five mine isolates. The Clusters of Orthologous Group (COG) annotation showed that the "amino acid transport and metabolism" [E] was the most predominant functional category in all genomes. In addition, the KEEG pathways analysis also showed predicted genes for the biosynthetic pathways of most amino acids, indicating that amino acids could have an important role in the Ga leaching mechanism. The presence of effective resistance mechanisms to Ga and arsenic (As) was particularly important in GaAs bioleaching batch assays, and might explain the divergence in bioleaching efficiency among the bacterial strains. Rhodanobacter sp. B2A1Ga4 and Sphingomonas sp. A2-49 with higher resistance, mainly to As, were the most efficient bioleaching strains under these conditions. In bioleaching assays using cell-free spent medium Arthrobacter silviterrae A2-55 with lower As resistance outperformed all the other stains. Overall, higher efficiency in Ga leaching was obtained in bioleaching assays using GaAs when compared to GaN. [ABSTRACT FROM AUTHOR]

Gallium (Ga) is considered a high-tech Critical Metal, used in the manufacture of several microelectronic components containing either gallium arsenide (GaAs) or gallium nitride (GaN). The current high demand for this critical metal urges the development of effective recovery processes from secondary resources such as mine tailings or electronic recycling material. The importance of bioleaching as a biotechnological process to recover metals prompted this study, where an integrative approach combining experimental and genomic analysis was undertaken to identify potential mechanisms involved in bioleaching ability and strategies to cope with high metal(loid)s concentrations in five mine isolates. The Clusters of Orthologous Group (COG) annotation showed that the “amino acid transport and metabolism” [E] was the most predominant functional category in all genomes. In addition, the KEEG pathways analysis also showed predicted genes for the biosynthetic pathways of most amino acids, indicating that amino acids could have an important role in the Ga leaching mechanism. The presence of effective resistance mechanisms to Ga and arsenic (As) was particularly important in GaAs bioleaching batch assays, and might explain the divergence in bioleaching efficiency among the bacterial strains. Rhodanobacter sp. B2A1Ga4 and Sphingomonas sp. A2-49 with higher resistance, mainly to As, were the most efficient bioleaching strains under these conditions. In bioleaching assays using cell-free spent medium Arthrobacter silviterrae A2-55 with lower As resistance outperformed all the other stains. Overall, higher efficiency in Ga leaching was obtained in bioleaching assays using GaAs when compared to GaN.

Humus formation in compost is key to improving the quality of organic fertilizers. Soil has the potential to promote humus formation due to characteristics such as porousness and large amounts of nutrients, but the mechanisms by which soil drives humus formation are unknown. The study intended to reveal the effects of soil addition on humification and microbial metabolism during composting and to investigate the mechanisms by which soil drives humification. The results showed that hemicellulose and cellulose contents were reduced by 4.67, 11.8 % and 5.85, 6.26 % in compost with Paddy soil (PS) and Laterite soil (LS) addition, respectively, compared to control group. Humus and humic acid increased by 38.1, 38.8 % and 60.6, 77.8 % after composting. Soil addition significantly enriched the hydrolytic bacteria Corynebacterium and fungi Thermomyces , raising the efficiency of organic matter conversion and symbiotic metabolic network complexity. Soil addition improved carbohydrate and amino acid metabolism, facilitating polyphenol synthesis and amino acids polymerization, and enhanced the humus through the polyphenol humification pathway. In summary, by regulating the microbial metabolism during composting, soil can successfully encourage humus formation. This study offers a new option and method for quick humification. [Display omitted] • Innovatively add soil to promote composting maturity. • Paddy and Laterite soil (PS, LS) promoted humification and enhanced stability. • PS and LS increased the complexity of the symbiotic metabolic network. • PS and LS raised humus through polyphenol humification pathway. [ABSTRACT FROM AUTHOR]

Chryseobacterium indologenes is a non-glucose-fermenting Gram-negative bacillus. This emerging multidrug resistant opportunistic nosocomial pathogen can cause severe infections in neonates and immunocompromised patients. This study aimed to present the first detailed draft genome sequence of a multidrug-resistant C. indologenes strain isolated from the cerebrospinal fluid of an infant hospitalized at the Neonatal Intensive Care Unit of Brazilian Tertiary Hospital. We first analyzed the susceptibility of C. indologenes strain to different antibiotics using the VITEK 2 system. The strain demonstrated an outstanding resistance to all the antibiotic classes tested, including β-lactams, aminoglycosides, glycylcycline, and polymyxin. Next, C. indologenes was whole-genome-sequenced, annotated using Prokka and Rapid Annotation using Subsystems Technology (RAST), and screened for orthologous groups (EggNOG), gene ontology (GO), resistance genes, virulence genes, and mobile genetic elements using different software tools. The draft genome contained one circular chromosome of 4,836,765 bp with 37.32% GC content. The genomic features of the chromosome present numerous genes related to cellular processes that are essential to bacteria. The MDR C. indologenes revealed the presence of genes that corresponded to the resistance phenotypes, including genes to β-lactamases (blaIND–13, blaCIA–3, blaTEM–116, blaOXA–209, blaVEB–15), quinolone (mcbG), tigecycline (tet(X6)), and genes encoding efflux pumps which confer resistance to aminoglycosides (RanA/RanB), and colistin (HlyD/TolC). Amino acid substitutions related to quinolone resistance were observed in GyrA (S83Y) and GyrB (L425I and K473R). A mutation that may play a role in the development of colistin resistance was detected in lpxA (G68D). Chryseobacterium indologenes isolate harbored 19 virulence factors, most of which were involved in infection pathways. We identified 13 Genomic Islands (GIs) and some elements associated with one integrative and conjugative element (ICEs). Other elements linked to mobile genetic elements (MGEs), such as insertion sequence (ISEIsp1), transposon (Tn5393), and integron (In31), were also present in the C. indologenes genome. Although plasmids were not detected, a ColRNAI replicon type and the most resistance genes detected in singletons were identified in unaligned scaffolds. We provided a wide range of information toward the understanding of the genomic diversity of C. indologenes, which can contribute to controlling the evolution and dissemination of this pathogen in healthcare settings.

The Gram-positive bacterium Bacillus subtilis is extensively used in the industry for the secretory production of proteins with commercial value. To further improve its performance, this microbe has been the subject of extensive genome engineering efforts, especially the removal of large genomic regions that are dispensable or even counterproductive. Here, we present the genome-reduced B. subtilis strain IIG-Bs-27-39, which was obtained through systematic deletion of mobile genetic elements, as well as genes for extracellular proteases, sporulation, flagella formation, and antibiotic production. Different from previously characterized genome-reduced B. subtilis strains, the IIG-Bs-27-39 strain was still able to grow on minimal media. We used this feature to benchmark strain IIG-Bs-27-39 against its parental strain 168 with respect to heterologous protein production and metabolic parameters during bioreactor cultivation. The IIG-Bs-27-39 strain presented superior secretion of difficult-to-produce staphylococcal antigens, as well as higher specific growth rates and biomass yields. At the metabolic level, changes in byproduct formation and internal amino acid pools were observed, whereas energetic parameters such as the ATP yield, ATP/ADP levels, and adenylate energy charge were comparable between the two strains. Intriguingly, we observed a significant increase in the total cellular NADPH level during all tested conditions and increases in the NAD + and NADP(H) pools during protein production. This indicates that the IIG-Bs-27-39 strain has more energy available for anabolic processes and protein production, thereby providing a link between strain physiology and production performance. On this basis, we conclude that the genome-reduced strain IIG-Bs-27-39 represents an attractive chassis for future biotechnological applications.

Fermentative features of doenjang-meju, a traditional Korean soybean brick, were investigated over 45 days via genome-centered metatranscriptomics. The pH value rapidly decreased within 10 days and successively increased after 20 days, along with an initial bacterial growth, including lactic acid bacteria, and subsequent fungal growth, suggesting their association. Polysaccharides and lipids underwent degradation, and amino acids, free sugars, and organic acids increased during the early stage. Metagenome analysis identified Aspergillus , Bacillus , Enterococcus , Staphylococcus , and Leuconostoc as major microbes, which were isolated and genome-sequenced. Metatranscriptomic analysis revealed the major roles of Bacillus and Enterococcus during the early period, shifting to Aspergillus dominance after 10 days. Metabolic pathway reconstruction and transcriptional analysis reveal that Aspergillus primarily decomposed polysaccharides to free sugars; Aspergillus and Bacillus metabolized lipids, free sugars, and organic acids generated by Enterococcus ; and Aspergillus and Bacillus were instrumental in amino acid metabolism: their contributions varied by compounds and pathways., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

PET/CT is an hybrid technique which allows both morfological and metabolical evalutaion. Three different morphometeabolical patterns are presented which reflect the evolutive phases of the COVID-19. This findings may help the clinician determine the correct treatment and security measure that need to be taken aaccording to the phase of the disease.

Classic galactosemia (CG) is an autosomal recessive disorder that impacts close to 1/50000 live births in the United States, with varying prevalence in other countries. Following exposure to milk, which contains high levels of galactose, affected infants may experience rapid onset and progression of potentially lethal symptoms. With the benefit of early diagnosis, generally by newborn screening, and immediate and lifelong dietary restriction of galactose, the acute sequelae of disease can be prevented or resolved. However, long‐term complications are common, and despite many decades of research, the bases of these complications remain unexplained. As a step toward defining the underlying pathophysiology of long‐term outcomes in CG, we applied an untargeted metabolomic approach with mass spectrometry and dual liquid chromatography, comparing thousands of small molecules in plasma samples from 183 patients and 31 controls. All patients were on galactose‐restricted diets. Using both univariate and multivariate statistical methods, we identified 252 differentially abundant features from anion exchange chromatography and 167 differentially abundant features from C18 chromatography. Mapping these discriminatory features to putative metabolites and biochemical pathways revealed 14 significantly perturbed pathways; these included multiple redox, amino acid, and mitochondrial pathways, among others. Finally, we tested whether any discriminatory features also distinguished cases with mild vs more severe long‐term outcomes and found multiple candidates, of which one achieved false discovery rate‐adjusted q < 0.1. These results extend substantially from prior targeted studies of metabolic perturbation in CG and offer a new approach to identifying candidate modifiers and targets for intervention. [ABSTRACT FROM AUTHOR]

Members of the family Vibrionaceae are metabolically versatile and ubiquitous in natural environments, with extraordinary genome feature of two chromosomes. Here we reported the complete genome of Paraphotobacterium marinum NSCS20N07DT, a recently described novel genus-level species in the family Vibrionaceae. It contained two circular chromosomes with a size of 2,593,992 bp with G+C content of 31.2 mol%, and a plasmid with a size of 5,539 bp. The larger chromosome (Chr. I) had a genome size of 1,426,504 bp with G+C content of 31.6 mol%, and the smaller one (Chr. II) had a genome size of 1,161,949 bp with G+C content of 30.8 mol%. The two chromosomes have strikingly similar G+C contents with difference of

BackgroundThe aim of this study was to examine the clinical characteristics of adrenal incidentalomas discovered by computed tomography (CT) and to investigate metabolic features of subclinical Cushing's syndrome (SCS) in patients with adrenal incidentalomas in a tertiary hospital in Korea.MethodsThis retrospective study examined the clinical aspects of 268 patients with adrenal incidentalomas discovered by CT at Soonchunhyang University Bucheon Hospital. Clinical data and endocrine function of the patients as well as histological findings were obtained from medical records, while anatomic characteristics were analyzed by reviewing imaging studies. Hormonal tests for pheochromocytoma, Cushing's syndrome, and aldosterone-secreting adenoma were performed.ResultsMost (n=218, 81.3%) cases were nonfunctioning tumors. Of the 50 patients with functioning tumors (18.7%), 19 (7.1%) were diagnosed with SCS, nine (3.4%) with overt Cushing's syndrome, 12 (4.5%) with primary aldosteronism, and 10 (3.7%) with pheochromocytoma. Malignant tumors (both primary and metastatic) were rare (n=2, 0.7%). Body mass index, fasting glucose, hemoglobin A1c, and total cholesterol were significantly higher in patients with SCS in comparison with those with nonfunctioning tumors. The prevalence of type 2 diabetes mellitus and hypertension were significantly higher in patients with SCS compared with those with nonfunctioning tumors.ConclusionFunctioning tumors, especially those with subclinical cortisol excess, are commonly found in patients with adrenal incidentalomas, although malignancy is rare. In addition, patients with SCS in adrenal incidentalomas have adverse metabolic and cardiovascular profiles.

Background: Thyroid eye disease (TED) is the most frequent orbital disease in adults and is characterized by the accumulation of orbital adipose tissue (OAT). It can lead to eyelid retraction or even vision loss. Orbital decompression surgery serves as the primary treatment for inactive TED by removing the excess OAT. However, there is a lack of alternative treatments to surgery due to the unclear understanding of the pathogenesis, particularly the metabolic features. Accordingly, our study was implemented to explore the content and features of metabolites of OATs from TED patients., Method: The OATs used in the current study were obtained from the orbital decompression surgery of seven patients with inactive TED. We also collected control OATs from eye surgical samples of five individuals with no history of autoimmune thyroid diseases, TED, or under non-inflammatory conditions. The liquid chromatography mass spectrometer was used for the measurements of the targeted metabolites. Afterwards, we performed differential metabolite assay analysis and related pathway enrichment analysis., Results: In our study, a total of 149 metabolite profiles were detected in all participants. There were significant differences in several metabolite profiles between the TED group and the control group, mainly including uric acid, oxidized glutathione, taurine, dGMP, oxidized glutathione 2, uracil, hexose-phosphate, 1-methylnicotinamide, D-sedoheptulose 1,7-bisphosphate, and uridine 5'-monophosphate (all p -value < 0.05). The TED-related pathways identified included purine metabolism, beta-alanine metabolism, glutathione metabolism ( p -values < 0.05). Our study found overlaps and differences including uric acid and uracil, which are in accordance with metabolites found in blood of patients with TED from previous study and several newly discovered metabolite by our study such as hexose-phosphate, 1-methylnicotinamide, D-sedoheptulose 1,7-bisphosphate, compared to those tested from blood, OAT, or urine samples reported in previous studies., Conclusion: The findings of our study shed light on the metabolic features of OAT in individuals with TED. These results may help identify new treatment targets for TED, providing potential avenues for developing alternative treatments beyond ophthalmic surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Du, Wang, Yang, Hu, Liu, Jian, Wang, Zhang, Chen, Wang and Zhang.)

[Display omitted] • Biochar addition significantly promoted humus formation. • Biochar addition changed fungal composition, diversities and functions. • Biochar addition accelerated the metabolisms and metabolites for humus formation. Humus formation of composting is crucial for improving organic fertilizer quality. Biochar has been found to be a low-cost, eco-friendly and effective promoter for humus formation, while the mechanisms underlying the biochar-driven humus formation during composting remain unknown. The present study was aimed to explore the effect of biochar addition on humus formation by integrated analyses of fungal communities, functional genes and metabolic features during composting using the advanced techniques of fluorescence spectrometry, high throughput sequencing, metagenomics, and metabolomics. The efficiencies of fulvic acid and humic acid formation were increased by 17.4 % and 39.4 %, respectively, under biochar addition relative to the control at the mature phase. Biochar addition significantly increased temperature, lignocellulose degradation and the activities of urease, peroxidase, manganese peroxidase and lignin peroxidase, and altered the fungal community composition and diversity with the latter significantly correlated with humic acid content. The altered fungal community subsequently resulted in the stimulation of fungal function of Wood Saprotroph and expression of CAZyme genes at the thermophilic and mature phases. Ultimately, biochar addition significantly enhanced the Xenobiotics metabolism (Bisphenol metabolism and Quinone biosynthesis) and Amino acid metabolism (Tryptophan metabolism and Tyrosine metabolism), which were responsible for humus formation via producing metabolic compounds such as quinolines, phenolics and aromatic amino acids at the mature phase. Our findings suggest that biochar addition can effectively stimulate humus formation by selectively regulating fungal communities and metabolic features during composting, so that benefits the improvement of soil fertility and health upon the organic fertilizer application. [ABSTRACT FROM AUTHOR]

Candida auris is an emerging human pathogen, associated with antifungal drug resistance and hospital candidiasis outbreaks. In this work, we present iRV973, the first reconstructed Genome-scale metabolic model (GSMM) for C. auris. The model was manually curated and experimentally validated, being able to accurately predict the specific growth rate of C. auris and the utilization of several sole carbon and nitrogen sources. The model was compared to GSMMs available for other pathogenic Candida species and exploited as a platform for cross-species comparison, aiming the analysis of their metabolic features and the identification of potential new antifungal targets common to the most prevalent pathogenic Candida species. From a metabolic point of view, we were able to identify unique enzymes in C. auris in comparison with other Candida species, which may represent unique metabolic features. Additionally, 50 enzymes were identified as potential drug targets, given their essentiality in conditions mimicking human serum, common to all four different Candida models analysed. These enzymes represent interesting drug targets for antifungal therapy, including some known targets of antifungal agents used in clinical practice, but also new potential drug targets without any human homolog or drug association in Candida species., (© The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.)

The clinical symptoms of diabetic neuropathy (DN) manifest in a time dependent manner as a positive symptoms (i. e. pain, hypersensitivity, tingling, cramps, cold feet etc.) during its early stages and by a loss of function (i. e. loss of sensory perception, delayed wound healing etc.) predominating in the later stages. Elevated blood glucose alone cannot explain the development and progression of DN and the lowering of blood glucose is insufficient in preventing and/or reversing neuropathy in patients with type 2 diabetes. Recently it has been shown that the endogenous reactive metabolite methylglyoxal (MG) can contribute to the gain of function via posttranslational modification in DN of neuronal ion channels involved in chemosensing and action potential generation in nociceptive nerve endings. Dicarbonyls, such as MG, that are elevated in diabetic patients, modify DNA as well as extraand intracellular proteins, leading to the formation of advanced glycation endproducts (AGEs). Increased formation of AGEs leads to increased cellular stress, dysfunction and ultimately cell death. The interaction of AGE-modified proteins through cell surface receptors, such as RAGE, can lead to increased cellular activation and sustained inflammatory responses, which are the molecular hallmarks of the later, degenerative, stages of DN. The direct and indirect effects of dicarbonyls on nerves or neuronal microvascular network provides a unifying mechanism for the development and progression of DN. Targeting the accumulation of MG and/or prevention of RAGE interactions may therefore provide new, more effective, therapeutic approaches for the treatment of DN. [ABSTRACT FROM AUTHOR]

Background: Since obesity and its associated co-morbidities do not only have effect on the individual patient, but also on society and the health system, it is of great importance to investigate this lifestyle-disease. The rationale of this study was to distinguish metabolically healthy from unhealthy overweight/obese patients as compared to healthy normal weight children and adolescents by means of a comprehensive anthropometric, laboratory and sonomorphological vascular assessment. Material and methods: 299 study participants were derived from the prospective, observational study STYJOBS/EDECTA (STYrian Juvenile Obesity Study/Early DEteCTion of Arteriosclerosis). Standard anthropometric data were obtained for each subject. This study comprised different diagnostic steps: extended anthropometry (Lipometer ® ), carotid artery ultrasound, various laboratory measurements, blood pressure measurement, oral glucose tolerance test. Ow/ob juveniles were classified as "metabolically healthy" (no laboratory criteria of metabolic syndrome fulfilled) vs. "metabolically unhealthy" (⩾ 3 criteria of metabolic syndrome). Results underwent statistical evaluation, including t-test or Mann- Whitney U-test, regression analysis and a p-value < 0.05 was considered statistically signifi cant. Results and Discussion: In the study's central European cohort only about 16 % (n = 48/299) of the overweight/obese juveniles can be regarded as metabolically healthy. About 36 % (n = 108/299) of the overweight/obese patients fulfilled the criteria for metabolic syndrome. High visceral fat stores (p < 0.001) and their clinical surrogate waist circumference (p < 0.001) determine an adverse metabolic phenotype. Several parameters, including uric acid (p < 0.001), adiponectin (p < 0.05), insulin resistance (HOMA-Index, p < 0.001), nuchal SAT thickness (p < 0.001), arteriosclerosis of the carotids (p < 0.001), and others are responsible for the distinction between metabolically healthy and unhealthy juveniles. Nevertheless, "healthy obesity" only defines a sub-phenotype of a disease effecting rising numbers of young patients. Conclusion: Since obesity in children and adolescents is not a consistent entity, it remains crucial to differ between metabolically healthy and unhealthy obese children in order to achieve appropriate intervention and prevention for our patients. [ABSTRACT FROM AUTHOR]

Background: A low-T3 syndrome is observed in chronic diseases, but its treatment is still debated. Chronic obstructive pulmonary disease (COPD) has not been conclusively studied under this aspect. COPD is a complex condition, which cannot be considered a lung-related disorder, but rather a systemic disease also associated to increased oxidative stress. We evaluated thyroid hormones and antioxidant systems, the lipophilic Coenzyme Q10 (CoQ10 ) and total antioxidant capacity (TAC) in COPD patients to reveal the presence of a low-T3 syndrome in COPD and investigate the correlation between thyroid hormones, lung function parameters and antioxidants. Methods: We studied: 32 COPD patients and 45 controls, evaluating thyrotropin (TSH), freetriiodotyronine (fT3 ), free-tetraiodotyronine (fT4 ), CoQ10 (also corrected for cholesterol) and TAC. CoQ10 was assayed by HPLC; TAC by the metmyoglobin- ABTS method and expressed as latency time (LAG) in radical species appearance. Results: We found significantly lower LAG values, fT3 and fT4 levels and significantly higher TSH in COPD patients vs. controls. LAG values significantly correlated with fT3 concentration. 12 out of 32 patients exhibited fT3 levels lower than normal range. So we divided COPD patients in 2 groups on the basis of the fT3 concentration (normal fT3 COPD and low fT3 COPD). We observed lower LAG values in normal fT3 -COPD, compared to healthy subjects, with a further significant reduction in low fT3 -COPD patients. Moreover higher TSH concentration was present in normal fT3 -COPD, compared to healthy subjects, with a further significant increase in low fT3 -COPD patients. CoQ10 /cholesterol ratio was higher in low fT3 -COPD vs. normal fT3 -COPD, with a nearly significant difference. Conclusions: These data seem to indicate an increased oxidative stress in low fT3 -COPD and a role of fT3 in modulating antioxidant systems. However low fT3 levels are joined to metabolic indexes of true hypothyroidism, suggesting that elevated CoQ10 expresses a reduced tissue utilization. These data might suggest the need of thyroid replacement therapy in such a condition. [ABSTRACT FROM AUTHOR]