NLRC4 methylation and its response to intravenous immunoglobulin therapy in Kawasaki disease: a case control study.

BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis accompanied by many systemic physiological and biochemical changes. Elucidating its molecular mechanisms is crucial for diagnosing and developing effective treatments. NLR Family CARD Domain Containing 4 (NLRC4) encodes the key components of inflammasomes that function as pattern recognition receptors. The purpose of this study was to investigate the potential of NLRC4 methylation as a biomarker for KD. METHODS: In this study, pyrosequencing was utilized to analyze NLRC4 promoter methylation in blood samples from 44 children with initial complete KD and 51 matched healthy controls. Methylation at five CpG sites within the NLRC4 promoter region was evaluated. RESULTS: Compared to controls, NLRC4 methylation significantly decreased in KD patients (CpG1: p = 2.93E-06; CpG2: p = 2.35E-05; CpG3: p = 6.46E-06; CpG4: p = 2.47E-06; CpG5: p = 1.26E-05; average methylation: p = 5.42E-06). These changes were significantly reversed after intravenous immunoglobulin (IVIG) treatment. ROC curve analysis demonstrated remarkable diagnostic capability of mean NLRC4 gene methylation for KD (areas under ROC curve = 0.844, sensitivity = 0.75, p = 9.61E-06, 95% confidence intervals were 0.762-0.926 for mean NLRC4 methylation). In addition, NLRC4 promoter methylation was shown to be significantly negatively correlated with the levels of central granulocyte percentage, age, mean haemoglobin quantity and mean erythrocyte volume. Besides, NLRC4 promoter methylation was positively correlated with lymphocyte percentage, lymphocyte absolute value. CONCLUSIONS: Our work revealed the role of peripheral NLRC4 hypomethylation in KD pathogenesis and IVIG treatment response, could potentially serve as a treatment monitoring biomarker, although its precise functions remain to be elucidated.

Fabrication of six-atom Pd clusters regulated with different short ligands and their surface structure-dependent catalytic activities.

As model catalysts, it is necessary to study the relationship between the structure and properties of ultra-small metal nanoclusters (MNCs) and to reduce their steric hindrance as much as possible, e.g. preparing ultrasmall MNCs protected by ultra-short ligands. However, it is challenging to attain various MNCs with the same cores but different surface stabilizing ligands. Additionally, shortening the chains of protecting ligands will lead to larger MNC cores. Here, four different Pd NCs (Pd6(SC4H9)12, Pd6(SC8H17)12, Pd6(SC6(C2)H17)12 and Pd6(SC6H13)12) were successfully synthesized by a slow synthesis process. All these clusters consist of six Pd atoms and are stabilized by 12 thiols with different chain lengths and steric hindrance. The catalytic properties of the as-prepared Pd6 NCs were evaluated using the catalytic reduction of p-nitroaniline to p-phenylenediamine as a model reaction. The outcomes indicated that shortening the chain length of the protecting thiols could enhance the catalytic activity of the Pd6 NCs. Notably, stable and active ultra-small Pd6 clusters stabilized by ultra-short ligands (HSC4H9) were successfully synthesized. Although the performance of Pd6(SC4H9)12 clusters protected by the ultra-short thiols is lower than that of commercial palladium on carbon (Pd/C), they display higher stability. Interestingly, the activity of Pd6 NCs protected by ethyl-branched alkane thiols is also better than that of Pd6 NCs protected by the alkane thiol ligands with the same chain length or the same number of carbon numbers. This work provides clear evidence that the catalytic activity of atomically precise MNCs can be controlled by regulating the surface stabilizing ligands.

Composition and dynamics of intestinal fungi during the postnatal 2 months of very low birth weight infants.

It has been found that intestinal fungi play a role in the composition of the intestinal microecology and in the formation and development of the immunity during childhood. We investigated the gut fungi composition of preterm infants to analysis composition and dynamics of intestinal fungi during the postnatal 2 months of very low birth weight infants. We collected feces from 34 very low birth weight infants (VLBWI) and 28 preterm infants with birth weight >1500 g. We extracted total fungal DNA from feces and analyzed the composition of gut fungus through ITS sequencing. The fungal detectable rate in the experimental group peaked on day 3 (85.19%), then gradually decreased and started to show an increasing trend again by day 28. There were significant differences in the alpha diversity of intestinal fungus between VLBWI and controls, and the VLBWI had its own characteristics at different time points in richness and diversity. A total of 10 phylums and 342 genera were identified in all VLBWI samples. The dominant fungal phylum of the VLBWI group is Ascomycota (50.3%)and Basidiomycota (48.8%). The functional metabolic activity of the experimental group was lower than that of the control group. CONCLUSION: The composition and abundance of VLBWI intestinal fungal showed several alterations during the first 2 months of life. The prediction of gut microbiota function suggests that intestinal metabolic function may be altered in VLBWI. WHAT IS KNOWN: • A limited number of studies has been found that symbiont fungi may be able to calibrate host immunological responses, promote development of peripheral lymphoid organs, promote T cell responses, and even may be associated with the development of certain diseases, such as inflammatory bowel disease (IBD), NEC, and allergic diseases. However, previous studies on intestinal microecology have mainly focused on adults while neglecting the role of fungi in the gut of children due to the much lower abundance of intestinal fungi than bacteria, limitations of techniques for detecting fungi, the difficulty of obtaining samples, and the absence of largescale reference databases. WHAT IS NEW: • In recent years, the discovery and development of fungal detection technologies such as 18s rDNA sequencing technology, Internal Transcribed Spacer(ITS), and DNA fingerprinting technology have further broadened the perspective on the impact of intestinal fungal exposure in early life.

Changes in Gut Microbiota at 1-60 Days in 92 Preterm Infants in a Neonatal Intensive Care Unit Using 16S rRNA Gene Sequencing.

BACKGROUND Neonatal gut diversity is influenced by birth conditions and probiotic/antibiotic use. The gut microbiota affects brain development, immunity, and risk of diseases. Preterm infants, especially in neonatal intensive care units (NICUs), have different gut flora from full-term infants, suggesting in utero microbial colonization. This study examined gut microbiota changes in 92 NICU preterm infants in China. MATERIAL AND METHODS We collected data on 92 preterm infants admitted to the NICU immediately after birth, and fecal samples were collected on days 1, 3, 7, 14, 21, 28, and 60. We analyzed changes in intestinal bacteria through 16S rRNA sequencing, predicted the change in gut microbiota function over time, and compared the effects of main feeding modality on the intestinal bacteria of preterm infants. RESULTS At the phylum level, the top 5 phyla in total accounted for 99.69% of the abundance, in decreasing order of abundance: Proteobacteria, Firmicutes, Actinobacteria, Tenericutes, and Bacteroidetes. At the genus level, the top 10 genera in terms of abundance accounted for a total of 90.90%, in decreasing order of abundance: Pseudomonas, Staphylococcus, Klebsiella, Escherichia-Shigella, unclassified Enterobacteriaceae, Staphylococcus, Clostridium-sensu-stricto-1, Streptococcus, Sphingomonas, and Ureaplasma. The abundance of Proteobacteria and Pseudomonas showed a decreasing trend at first, reached a minimum at day 14, and then an increasing trend, while the opposite trend was observed for Firmicutes. The metabolic function of the bacterial community changed greatly at different time points. The abundance of Proteobacteria at the phylum level and Streptococcus at the genus level in formula-fed infants were significantly higher than in breast-fed infants. CONCLUSIONS Between 1 and 60 days, the gut microbiome in preterm infants in the NICU changed with changes in feeding patterns, with the main gut bacteria being from the phyla, Proteobacteria, and Pseudomonas.

Iodide-Mediated Etching of Gold Nanostar for the Multicolor Visual Detection of Hydrogen Peroxide.

A multicolor visual method for the detection of hydrogen peroxide (H2O2) was reported based on the iodide-mediated surface etching of gold nanostar (AuNS). First, AuNS was prepared by a seed-mediated method in a HEPES buffer. AuNS shows two different LSPR absorbance bands at 736 nm and 550 nm, respectively. Multicolor was generated by iodide-mediated surface etching of AuNS in the presence of H2O2. Under the optimized conditions, the absorption peak Δλ had a good linear relationship with the concentration of H2O2 with a linear range from 0.67~66.67 µmol L-1, and the detection limit is 0.44 µmol L-1. It can be used to detect residual H2O2 in tap water samples. This method offered a promising visual method for point-of-care testing of H2O2-related biomarkers.