Background
Childhood asthma is a multifactorial inflammatory condition of the airways, associated with specific changes in respiratory microbiome and circulating metabolome.
Methods
To explore the ...functional capacity of asthmatic microbiome and its intricate connection with the host, we performed shotgun sequencing of airway microbiome and untargeted metabolomics profiling of serum samples in a cohort of children with mite‐sensitized asthma and non‐asthmatic controls.
Results
We observed higher gene counts and sample‐to‐sample dissimilarities in asthmatic microbiomes, indicating a more heterogeneous community structure and functionality among the cases than in controls. Moreover, we identified airway microbial species linked to changes in circulating metabolites and IgE responses of the host, including a positive correlation between Prevotella sp oral taxon 306 and dimethylglycine that were both decreased in patients. Several control‐enriched species (Eubacterium sulci, Prevotella pallens, and Prevotella sp oral taxon 306) were inversely correlated with total and allergen‐specific IgE levels. Genes related to microbial carbohydrate, amino acid, and lipid metabolism were differentially enriched, suggesting that changes in microbial metabolism may contribute to respiratory health in asthmatics. Pathway modules relevant to allergic responses were differentially abundant in asthmatic microbiome, such as enrichments for biofilm formation by Pseudomonas aeruginosa, membrane trafficking, histidine metabolism, and glycosaminoglycan degradation, and depletions for polycyclic aromatic hydrocarbon degradation. Further, we identified metagenomic and metabolomic markers (eg, Eubacterium sulci) to discriminate cases from the non‐asthmatic controls.
Conclusions
Our dual‐omics data reveal the connections between respiratory microbes and circulating metabolites perturbed in mite‐sensitized pediatric asthma, which may be of etiological and diagnostic implications.
This study demonstrates shotgun sequencing of airway microbiome and untargeted metabolomics profiling of serum samples in children with mite‐sensitized asthma and non‐asthmatic controls. Integrative analysis identifies specific airway dysbiosis at the species level and its associated functional shift in strong associations with circulating metabolites and IgE responses to mites. Overall, dual‐omics integration reveals microbe‐metabolite connections perturbed in mite‐sensitized pediatric asthma.
Abbreviations: KEGG, Kyoto Encyclopedia of Genes and Genomes; AUC, area under the receiver operating characteristic curve
Recently, deep learning (DL) has emerged as a revolutionary and versatile tool transforming industry applications and generating new and improved capabilities for scientific discovery and model ...building. The adoption of DL in hydrology has so far been gradual, but the field is now ripe for breakthroughs. This paper suggests that DL-based methods can open up a complementary avenue toward knowledge discovery in hydrologic sciences. In the new avenue, machine-learning algorithms present competing hypotheses that are consistent with data. Interrogative methods are then invoked to interpret DL models for scientists to further evaluate. However, hydrology presents many challenges for DL methods, such as data limitations, heterogeneity and co-evolution, and the general inexperience of the hydrologic field with DL. The roadmap toward DL-powered scientific advances will require the coordinated effort from a large community involving scientists and citizens. Integrating process-based models with DL models will help alleviate data limitations. The sharing of data and baseline models will improve the efficiency of the community as a whole. Open competitions could serve as the organizing events to greatly propel growth and nurture data science education in hydrology, which demands a grassroots collaboration. The area of hydrologic DL presents numerous research opportunities that could, in turn, stimulate advances in machine learning as well.
Chronic kidney disease (CKD) is a serious healthcare dilemma, associated with specific changes in gut microbiota and circulating metabolome. Yet, the functional capacity of CKD microbiome and its ...intricate relationship with the host metabolism at different stages of disease are less understood.
Here, shotgun sequencing of fecal samples and targeted metabolomics profiling of serum bile acids, short- and medium-chain fatty acids, and uremic solutes were performed in a cohort of CKD patients with different severities and non-CKD controls.
We identified that levels of 13 microbial species and 6 circulating metabolites were significantly altered across early to advanced stages or only in particular stage(s). Among these, Prevotella sp. 885 (decreased) was associated with urea excretion, while caproic acid (decreased) and p-cresyl sulfate (elevated) were positively and negatively correlated with the glomerular filtration rate, respectively. In addition, we identified gut microbial species linked to changes in circulating metabolites. Microbial genes related to secondary bile acid biosynthesis were differentially abundant at the early stage, while pathway modules related to lipid metabolism and lipopolysaccharide biosynthesis were enriched in the CKD microbiome at the advanced stage, suggesting that changes in microbial metabolism and host inflammation may contribute to renal health. Further, we identified metagenomic and metabolomic markers to discriminate cases of different severities from the controls, among which Bacteroides eggerthii individually was of particular value in early diagnosis.
Our dual-omics data reveal the connections between intestinal microbes and circulating metabolites perturbed in CKD, which may be of etiological and diagnostic importance.
The interplay of the gut microbes with gut-producing nephrotoxins and the renal progression remains unclear in large human cohort. Significant compositional and functional differences in the ...intestinal microbiota (by 16S rRNA gene sequencing) were noted among 30 controls and 92 (31 mild, 30 moderate and 31 advanced) patients at different chronic kidney disease (CKD) stages (discovery cohort). A core CKD-associated microbiota consisted of 7 genera (Escherichia_Shigella, Dialister, Lachnospiraceae_ND3007_group, Pseudobutyrivibrio, Roseburia, Paraprevotella and Ruminiclostridium) and 2 species (Collinsella stercoris and Bacteroides eggerthii) were identified to be highly correlated with the stages of CKD. Paraprevotella, Pseudobutyrivibrio and Collinsella stercoris were superior in discriminating CKD from the controls than the use of urine protein/creatinine ratio, even at early-stage of disease. The performance was further confirmed in a validation cohort comprising 22 controls and 76 peritoneal dialysis patients. Bacterial genera highly correlated with indoxyl sulfate and p-cresyl sulfate levels were identified. Prediction of the functional capabilities of microbial communities showed that microbial genes related to the metabolism of aromatic amino acids (phenylalanine, tyrosine, and tryptophan) were differentially enriched among the control and different CKD stages. Collectively, our results provide solid human evidence of the impact of gut-metabolite-kidney axis on the severity of chronic kidney disease and highlight a usefulness of specific gut microorganisms as possible disease differentiate marker of this global health burden.
Antrodia camphorata is an endemic mushroom in Taiwan. This study was designed to screen anti-inflammatory compounds from the methanolic extract of the mycelium of A. camphorata on nitric oxide (NO) ...production in RAW 264.7 cells induced by polyinosinic-polycytidylic acid (poly I:C), a synthetic analog of double-stranded RNA (dsRNA) known to be present in viral infection. A combination of bioactivity-guided isolation with an NMR-based identification led to the isolation of 4-acetylantroquinonol B (1), along with seven compounds. The structure of new compounds (4 and 5) was elucidated by spectroscopic experiments, including MS, IR, and NMR analysis. The anti-inflammatory activity of all isolated compounds was assessed at non-cytotoxic concentrations. 4-Acetylantroquinonol B (1) was the most potent compound against poly I:C-induced NO production in RAW 264.7 cells with an IC50 value of 0.57 ± 0.06 μM.
Neurons extend long axons that require maintenance and are susceptible to degeneration. Long-term integrity of axons depends on intrinsic mechanisms including axonal transport and extrinsic support ...from adjacent glial cells. The mechanisms of support provided by myelinating oligodendrocytes to underlying axons are only partly understood. Oligodendrocytes release extracellular vesicles (EVs) with properties of exosomes, which upon delivery to neurons improve neuronal viability in vitro. Here, we show that oligodendroglial exosome secretion is impaired in 2 mouse mutants exhibiting secondary axonal degeneration due to oligodendrocyte-specific gene defects. Wild-type oligodendroglial exosomes support neurons by improving the metabolic state and promoting axonal transport in nutrient-deprived neurons. Mutant oligodendrocytes release fewer exosomes, which share a common signature of underrepresented proteins. Notably, mutant exosomes lack the ability to support nutrient-deprived neurons and to promote axonal transport. Together, these findings indicate that glia-to-neuron exosome transfer promotes neuronal long-term maintenance by facilitating axonal transport, providing a novel mechanistic link between myelin diseases and secondary loss of axonal integrity.
Reciprocal interactions between neurons and oligodendrocytes are not only crucial for myelination, but also for long-term survival of axons. Degeneration of axons occurs in several human myelin ...diseases, however the molecular mechanisms of axon-glia communication maintaining axon integrity are poorly understood. Here, we describe the signal-mediated transfer of exosomes from oligodendrocytes to neurons. These endosome-derived vesicles are secreted by oligodendrocytes and carry specific protein and RNA cargo. We show that activity-dependent release of the neurotransmitter glutamate triggers oligodendroglial exosome secretion mediated by Ca²⁺ entry through oligodendroglial NMDA and AMPA receptors. In turn, neurons internalize the released exosomes by endocytosis. Injection of oligodendroglia-derived exosomes into the mouse brain results in functional retrieval of exosome cargo in neurons. Supply of cultured neurons with oligodendroglial exosomes improves neuronal viability under conditions of cell stress. These findings indicate that oligodendroglial exosomes participate in a novel mode of bidirectional neuron-glia communication contributing to neuronal integrity.
This meta-analysis aimed at investigating the efficacy of high-flow nasal oxygenation (HFNO) against hypoxemia in patients with obesity compared with conventional oxygenation therapy and non-invasive ...ventilation. Databases were searched from inception to August 2021. Studies involving peri- or post-procedural use of HFNO were included. The primary outcome was risk of hypoxemia, while the secondary outcomes included status of oxygenation and carbon dioxide elimination. Ten randomized controlled trials (RCTs) were included. We found that HFNO prolonged the safe apnea time at induction compared to control group mean difference (MD) = 73.88 s, p = 0.0004; 2 RCTs with no difference in risk of peri-procedural hypoxemia relative risk (RR) = 0.91, p = 0.64; 4 RCTs, minimum SpO2 (MD = 0.09%, p = 0.95; 4 RCTs), PaO2 (MD = - 8.13 mmHg, p = 0.86; 3 RCTs), PaCO2 (MD = - 6.71%, p = 0.2; 2 RCTs), EtCO2 (MD = - 0.28 mmHg, p = 0.8; 4 RCTs) between the two groups. HFNO also did not improve postprocedural PaO2/FiO2 ratio (MD = 41.76, p = 0.58; 2 RCTs) and PaCO2 (MD = - 2.68 mmHg, p = 0.07; 2 RCTs). This meta-analysis demonstrated that the use of HFNO may be associated with a longer safe apnea time without beneficial impact on the risk of hypoxemia, oxygenation, and CO2 elimination in patients with obesity. The limited number of trials warranted further large-scale studies to support our findings.
This meta-analysis aimed at investigating the effectiveness of laryngeal mask airway (LMA) against postoperative pharyngolaryngeal complications after thyroidectomy. MEDLINE, Cochrane Library, google ...scholar, and EMBASE databases were searched from inception through February, 2021, for randomized controlled trials (RCTs) comparing the incidence of pharyngolaryngeal complications following the use of LMA or endotracheal tube (ETT). Pooled results from seven RCTs involving 600 patients showed an association of LMA with a reduced risk of postoperative sore throat (POST) at 24 h risk ratio (RR) 0.75, p = 0.006, four trials, but not at 1 h and 48 h after thyroidectomy. POST severity and hoarseness risk were lower in the LMA group than the ETT group at 1 h, 24 h, and 48 h (all p < 0.05). Nevertheless, hoarseness severity was lower in the LMA group only at postsurgical 48 h standardized mean difference = - 0.35, p = 0.008, three trials. Moreover, the risk of emergence cough was lower in patients using LMA than those receiving ETT (RR = 0.14, p = 0.002, two trials). The two groups did not differ in the severity of dysphagia at postoperative 1 h, 24 h, and 48 h. This meta-analysis showed that LMA may be associated with fewer pharyngolaryngeal complications compared to ETT without airway impacts. The limited number of included studies warrants further research to support our findings.
Effects of pH (5, 7, or 9) and arginine level (0, 0.6%, 1.2%, or 1.8%, w/v) on the stabilization of emulsions prepared by a novel thermal-assisted stirring method were evaluated. The results of ...physical stability showed that thermal-assisted stirring was effective in manufacturing heat-insensitive o/w emulsions. As the arginine level increased, the emulsifying ability and the absolute zeta potential of each pH-treated group first increased significantly and then decreased significantly, reaching a maximum at 1.2% (w/v) addition. When pH increased, the emulsifying ability and the absolute zeta potential of each arginine-treated group increased significantly. The results of particle size, storage modulus, and loss modulus were in accordance with changes in the emulsifying ability and the zeta potential, which were confirmed by the microstructure. As a result, the emulsion prepared at pH 9 with 1.2% (w/v) arginine had the largest levels of emulsion stability and surface protein load (145.69 mg/m2). In conclusion, the major reason for the formation of heat-insensitive emulsions by thermal-assisted stirring might be attributed to a high level of surface protein load, and increasing pH and arginine addition might enhance the adsorption of gelatin-arginine complexes on the surface of oil droplets, thereby improving the stability of emulsions.
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•Thermal-assisted stirring could be used to produce gelatin-stabilized o/w emulsions.•The addition of arginine enhanced the physical stability of emulsions.•The addition of arginine increased the viscosity and reduced the loss modulus.•Arginine promoted the adsorption of gelatin on the surface of oil droplets.
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