Risk-prediction models for intravenous immunoglobulin resistance in Kawasaki disease: Risk-of-Bias Assessment using PROBAST.

BACKGROUND: The prediction model of intravenous immunoglobulin (IVIG) resistance in Kawasaki disease can calculate the probability of IVIG resistance and provide a basis for clinical decision-making. We aim to assess the quality of these models developed in the children with Kawasaki disease. METHODS: Studies of prediction models for IVIG-resistant Kawasaki disease were identified through searches in the PubMed, Web of Science, and Embase databases. Two investigators independently performed literature screening, data extraction, quality evaluation, and discrepancies were settled by a statistician. The checklist for critical appraisal and data extraction for systematic reviews of prediction modeling studies (CHARMS) was used for data extraction, and the prediction models were evaluated using the Prediction Model Risk of Bias Assessment Tool (PROBAST). RESULTS: Seventeen studies meeting the selection criteria were included in the qualitative analysis. The top three predictors were neutrophil measurements (peripheral neutrophil count and neutrophil %), serum albumin level, and C-reactive protein (CRP) level. The reported area under the curve (AUC) values for the developed models ranged from 0.672 (95% confidence interval [CI]: 0.631-0.712) to 0.891 (95% CI: 0.837-0.945); The studies showed a high risk of bias (ROB) for modeling techniques, yielding a high overall ROB. CONCLUSION: IVIG resistance models for Kawasaki disease showed high ROB. An emphasis on improving their quality can provide high-quality evidence for clinical practice. IMPACT STATEMENT: This study systematically evaluated the risk of bias (ROB) of existing prediction models for intravenous immunoglobulin (IVIG) resistance in Kawasaki disease to provide guidance for future model development meeting clinical expectations. This is the first study to systematically evaluate the ROB of IVIG resistance in Kawasaki disease by using PROBAST. ROB may reduce model performance in different populations. Future prediction models should account for this problem, and PROBAST can help improve the methodological quality and applicability of prediction model development.

Breastfeeding has no protective effects on the development of coronary artery lesions in Kawasaki disease: a retrospective cohort study.

BACKGROUND: Kawasaki disease (KD) is a self-limiting vasculitis with an unknown etiology. It has been reported that breastfeeding has a potential protective effect on KD development. However, whether breastfeeding has an effect on the development of coronary artery lesions (CALs) remains unclear. METHODS: We retrospectively reviewed the medical records of patients with the main diagnosis of KD hospitalized in our hospital from May 2017 to November 2018. Standardized telephone interviews were carried out to obtain feeding practices before KD was onset. RESULTS: Two hundred and ninety-three (51.6%) were exclusively breastfed, 223 (39.3%) were partially breastfed and 52 (9.2%) were formula fed. There were no significant differences in the characteristics regarding age, gender, incomplete KD, intravenous immunoglobulin (IVIG) resistance, and the laboratory variables among the three groups. With formula feeding as a reference, patients exclusively breastfed and partially breastfed seemed to have a higher incidence of CALs, even after adjusting confounders, but were not statistically significant. After grouping patients who were older than six months into formula feeding, partial breastfeeding for < 2 months, partial breastfeeding for ≥ 2 and < 4 months, partial breastfeeding for ≥ 4 and < 6 months and exclusively breastfeeding based on the length of breastfeeding, the results remained the same (P > 0.05). CONCLUSIONS: Breastfeeding has no protective effect on the development of CALs in KD.

Evaluation of Carotid Artery Elasticity in Early Stage of Kawasaki Disease by Two-Dimensional Speckle Tracking Imaging: A Pilot Study.

OBJECTIVES: Children with Kawasaki disease (KD) often develop impaired arterial function. The aim of the study was to assess the feasibility and efficacy of two-dimensional speckle tracking technique (2DSTI) for the evaluation of carotid artery elasticity in children with early-stage KD. METHODS: Children with KD (n = 97), age and sex-matched children with fever (n = 18), and healthy controls (n = 24) were included. Children with KD were subsequently divided into a coronary artery lesion group (CAL group, 27 cases) and a noncoronary artery lesion group (nCAL group, 70 cases) based on the results of echocardiography. The carotid circumferential peak strain (CCS) and carotid intima-media thickness (CIMT) for the children in each group were measured, and the laboratory indicators for each group were collected. RESULTS: The CCS of children with KD was lower than that of children with fever and healthy controls (P = .001 and .008), whereas CIMT was not significantly different among the groups. Moreover, the CCS of children in the CAL group was lower than that of children in the nCAL group and healthy controls (P = .001 and .000, respectively), whereas the CIMT of children in the CAL group was higher than that of children in the nCAL group (P = .014). In children with KD, CCS was negatively correlated with C-reactive protein (CRP) and alanine aminotransferase (ALT) (r = -.419, P = .001; and r = -.305, P = .003). However, CCS was negatively correlated with CRP (r = -.508, P = .007) but not ALT (r = -.176, P = .379) in children in the CAL group. CONCLUSION: CCS determined based on 2DSTI can reflect changes in the carotid artery elasticity function in the early stage of KD.

Reduced pectin content of cell walls prevents stress-induced root cell elongation in Arabidopsis.

The primary cell walls of plants provide mechanical strength while maintaining the flexibility needed for cell extension growth. Cell extension involves loosening the bonds between cellulose microfibrils, hemicelluloses and pectins. Pectins have been implicated in this process, but it remains unclear if this depends on the abundance of certain pectins, their modifications, and/or structure. Here, cell wall-related mutants of the model plant Arabidopsis were characterized by biochemical and immunohistochemical methods and Fourier-transform infrared microspectroscopy. Mutants with reduced pectin or hemicellulose content showed no root cell elongation in response to simulated drought stress, in contrast to wild-type plants or mutants with reduced cellulose content. While no association was found between the degrees of pectin methylesterification and cell elongation, cell wall composition analysis suggested an important role of the pectin rhamnogalacturonan II (RGII), which was corroborated in experiments with the RGII-modifying chemical 2ß-deoxy-Kdo. The results were complemented by expression analysis of cell wall synthesis genes and microscopic analysis of cell wall porosity. It is concluded that a certain amount of pectin is necessary for stress-induced root cell elongation, and hypotheses regarding the mechanistic basis of this result are formulated.

PEA: an integrated R toolkit for plant epitranscriptome analysis.

Motivation: The epitranscriptome, also known as chemical modifications of RNA (CMRs), is a newly discovered layer of gene regulation, the biological importance of which emerged through analysis of only a small fraction of CMRs detected by high-throughput sequencing technologies. Understanding of the epitranscriptome is hampered by the absence of computational tools for the systematic analysis of epitranscriptome sequencing data. In addition, no tools have yet been designed for accurate prediction of CMRs in plants, or to extend epitranscriptome analysis from a fraction of the transcriptome to its entirety. Results: Here, we introduce PEA, an integrated R toolkit to facilitate the analysis of plant epitranscriptome data. The PEA toolkit contains a comprehensive collection of functions required for read mapping, CMR calling, motif scanning and discovery and gene functional enrichment analysis. PEA also takes advantage of machine learning (ML) technologies for transcriptome-scale CMR prediction, with high prediction accuracy, using the Positive Samples Only Learning algorithm, which addresses the two-class classification problem by using only positive samples (CMRs), in the absence of negative samples (non-CMRs). Hence PEA is a versatile epitranscriptome analysis pipeline covering CMR calling, prediction and annotation and we describe its application to predict N6-methyladenosine (m6A) modifications in Arabidopsis thaliana. Experimental results demonstrate that the toolkit achieved 71.6% sensitivity and 73.7% specificity, which is superior to existing m6A predictors. PEA is potentially broadly applicable to the in-depth study of epitranscriptomics. Availability and implementation: PEA Docker image is available at https://hub.docker.com/r/malab/pea, source codes and user manual are available at https://github.com/cma2015/PEA. Supplementary information: Supplementary data are available at Bioinformatics online.

Kawasaki disease OX40-OX40L axis acts as an upstream regulator of NFAT signaling pathway.

BACKGROUND: We investigated a costimulatory molecule OX40-OX40L acting as an upstream regulator to regulate the nuclear factor of activated T cell (NFAT) in the acute phase of Kawasaki disease (KD). METHODS: One hundred and one samples were collected and divided into six groups: coronary artery lesion (KD-CAL) before intravenous immunoglobulin (IVIG), KD-CAL after IVIG, KD without CAL (KD-nCAL) before IVIG, KD-nCAL after IVIG, fever of unknown (Fou), and Healthy. In vitro OX40-stimulating and OX40L-inhibiting tests were conducted in Healthy and KD groups, respectively. Both the messenger RNA (mRNA) and protein expression levels of OX40, OX40L, NFAT1, and NFAT2 were investigated using quantitative reverse transcription PCR and immunoblotting assay, respectively. RESULTS: The mRNA and protein expression levels of NFAT1, NFAT2, OX40, and OX40L were significantly increased in KD-CAL and KD-nCAL groups before IVIG compared with Fou and Healthy groups and decreased after IVIG. A positive correlation was found between them in KD. In vitro OX40-stimulating test demonstrated the significantly increased mRNA and protein expression levels of NFAT1 and NFAT2 in the peripheral blood mononuclear cells of the Healthy group. Meanwhile, OX40L-inhibiting test showed significantly decreased expression levels of NFAT1 and NFAT2 in the KD group. CONCLUSION: OX40-OX40L acts as an upstream regulator in the NFAT signaling pathway involved in KD.

Evolution of intron-poor clades and expression patterns of the glycosyltransferase family 47.

MAIN CONCLUSION: A large-scale bioinformatics analysis revealed the origin and evolution of GT47 gene family, and identified two clades of intron-poor genes with putative functions in drought stress responses and seed development in maize. Glycosyltransferase family 47 (GT47) genes encode ß-galactosyltransferases and ß-glucuronyltransferases that synthesize pectin, xyloglucans and xylan, which are important components of the plant cell wall. In this study, we performed a systematic and large-scale bioinformatics analysis of GT47 gene family using 352 GT47 proteins from 15 species ranging from cyanobacteria to seed plants. The analysis results showed that GT47 family may originate in cyanobacteria and expand along the evolutionary trajectory to moss. Further analysis of 47 GT47 genes in maize revealed that they can divide into five clades with diverse exon-intron structures. Among these five clades, two were mainly composed with intron-poor genes, which may originate in the moss. Gene duplication analysis revealed that the expansion of GT47 gene family in maize was significantly driven from tandem duplication events and segmental duplication events. Significantly, almost all duplicated genes are intron-poor genes. Expression analysis indicated that several intron-poor GT47 genes may be involved in the drought stress response and seed development in maize. This work provides insight into the origin and evolutionary process, expansion mechanisms and expression patterns of GT47 genes, thus facilitating their functional investigations in the future.

Changes in Profiles of Kawasaki Disease Noted over Time in Suzhou, China.

OBJECTIVES: The purpose of the present study was to explore the changes in epidemiological, clinical and laboratory characteristics of Kawasaki disease (KD) over a 12-year period in this area. METHODS: The medical records of KD patients hospitalized in the Children's Hospital of Soochow University from January 2006 to December 2017 were retrospectively reviewed and analyzed. To elucidate the changes more clearly in these years, we divided all patients into three groups according to the time of admission, 5-year time intervals apart. RESULTS: We found the number of KD had increased in recent years, although the age compositions had some variances. The male-to-female ratio peaked in patients aged 6-11 months and then decreased with ages. Incidence rates of clinical characteristics were almost the same except for cervical lymphadenopathy. Significant differences were noted in percentage of neutrophils, albumin, C-reactive protein, erythrocyte sedimentation rate (ESR) and platelets. However, only ESR and platelets were significantly different after adjusting the days of disease onset. A trend showing a shorter fever duration before intravenous immunoglobulin treatment was also noted. CONCLUSIONS: The number of KD was increasing annually. Our results were indicative of a possibly changed etiology of the disease. However, further large-scale long-term surveillance is warranted.

Predictors of intravenous immunoglobulin-resistant Kawasaki disease in children: a meta-analysis of 4442 cases.

The purpose of this study was to identify the clinical features and laboratory factors that are predictive of intravenous immunoglobulin (IVIG)-resistant Kawasaki disease. Multiple databases were searched for relevant studies on IVIG-resistant Kawasaki disease published from January 2002 to April 2017. Eligible studies were retrieved by manual review of the references. Stata 12 was used for the meta-analysis. Weighted mean differences and odds ratios with 95% confidence intervals were calculated for several indices. Twenty-eight studies involving 26,260 patients comprising 4442 IVIG-resistant Kawasaki disease patients and 21,818 IVIG-sensitive Kawasaki disease patients were included. The meta-analysis showed that the erythrocyte sedimentation rate (ESR) in the IVIG-resistant group was significantly higher than that in the IVIG-sensitive group, and that platelet count and hemoglobin levels were significantly lower in the IVIG-resistant group. The patients with oral mucosa alterations, cervical lymphadenopathy, swelling of the extremities, polymorphous rash, and initial administration of IVIG ≤ 4.0 days after the onset of symptoms were more likely to be IVIG resistant. CONCLUSION: The initial administration of IVIG ≤ 4.0 days after the onset of symptoms increased ESR and decreased hemoglobin and platelet counts, oral mucosa alterations, cervical lymphadenopathy, swelling of the extremities, and polymorphous rash and are the risk factors for IVIG-resistant Kawasaki disease. What is Known: • Recent reports on this topic are about aspartate aminotransferase (AST), alanine aminotransferase (ALT), gammaglutamyl transferase, total bilirubin, white blood cells, platelets, erythrocyte sedimentation rate (ESR), polymorphonuclear leukocytes (PMN), C-reactive protein (CRP), pro-brain natriuretic peptide (BNP), albumin, and sodium as the risk factors in the IVIG-resistant Kawasaki disease; however, no studies have been published on clinical features as predictors of IVIG resistance. What is New: • This meta-analysis identified the clinical features, the initial administration of IVIG ≤ 4.0 days after the onset of symptoms, and much more comprehensive laboratory indicators, such as hemoglobin, as predictors of IVIG-resistant Kawasaki disease.

Evaluation of right ventricular myocardial strains by speckle tracking echocardiography after percutaneous device closure of atrial septal defects in children.

OBJECTIVES: The aim of this study was to clarify the influence of the ASD closure by occluder device on right ventricular acute and long-term changes in longitudinal systolic strains, by evaluating right ventricular wall deformation in children using speckle tracking echocardiography (STE). METHODS AND MATERIALS: We enrolled 30 children with ASDs and 40 controls in our study. The Amplatzer atrial defect occluder was used to close the ASDs. Transthoracic echocardiographic examinations were performed at 3 points in time: the day before closure, 1 day after closure, and 3 months after closure. The dimensions of the right atrium (RA) and the right ventricle (RV) were measured in apical four-chamber view. RV segmental longitudinal systolic strains (SLSs) and global longitudinal systolic strain (GLS) were obtained by two-dimensional STE. RESULTS: Before ASD closure, the RV SLSs and GLS were significantly higher than those of the controls. At 1 day after closure, the diameters of RA and RV decreased. All the RV SLSs and GLS decreased accordingly and were lower than the control values. At 3 months after closure, the apical free wall strain, all segments of septal strains, and GLS increased significantly compared with the values obtained at 1 day after closure. The diameters of the RA and RV decreased further as well. There were no significant differences in the strains compared with the control values, except for the free wall basal strain. CONCLUSIONS: Transcatheter device closure of ASDs improves RV strain indices and RV function recover to normal over 3 months.

Epidemiological and Clinical Characteristics of Kawasaki Disease and Factors Associated with Coronary Artery Abnormalities in East China: Nine Years Experience.

BACKGROUND: Because of the different genetic backgrounds, living environments and economic conditions, the epidemiologic, clinical characteristics and risk factors for coronary artery abnormalities (CAAs) in the Chinese population may differ among different parts of China. METHODS: We did a retrospective study to explore the clinical characteristics and risk factors for CAAs in east China between 2006 and 2014. RESULTS: There were 1016 patients during the study period. Of the 1004 patients who completed echocardiographic studies, 23.9% had CAAs. Sex, serum albumin, erythrocyte sedimentation rate (ESR),Mycoplasma pneumoniae(MP) infection, intravenous immunoglobulin (IVIG) started after the 10th day of illness and IVIG non-responders were independent risk factors associated with CAA. CONCLUSIONS: East China has a lower incidence of CAAs compared with southwest and northeast China, while similar to north China. Male gender, serum albumin, ESR, MP infection, IVIG started after the 10th day of illness and IVIG non-responders were predictive of CAA.

Transient changes in the ST-T waveform mimicking myocardial infarction in a child with near-drowning: a case report.

Drowning is a common cause of childhood morbidity and mortality worldwide. Anoxia, hypothermia, and metabolic acidosis are mainly responsible for this morbidity. Drowning may lead to multiple organ damage, especially cardiac damage, in cases in which severe hypothermia and hypoxemia occur. We report a case of a 4-year-old girl who was admitted to our hospital's Emergency Department because of drowning. She had elevated troponin I concentrations and ST-segment elevation with T wave inversion. However, cardiovascular computed tomography showed no obvious abnormalities in the coronary arteries. We suggest that cardiac damage in this situation is caused by coronary artery spasms. To the best of our knowledge, this is the first case of cardiac damage with electrocardiographic changes after drowning in a preschool child.

Analyzing the defense response mechanism of Atractylodes macrocephala to Fusarium oxysporum through small RNA and degradome sequencing.

Introduction: Fusarium oxysporum is a significant soil-borne fungal pathogen that affects over 100 plant species, including crucial crops like tomatoes, bananas, cotton, cucumbers, and watermelons, leading to wilting, yellowing, growth inhibition, and ultimately plant death. The root rot disease of A. macrocephala, caused by F. oxysporum, is one of the most serious diseases in continuous cropping, which seriously affects its sustainable development. Methods: In this study, we explored the interaction between A. macrocephala and F. oxysporum through integrated small RNA (sRNA) and degradome sequencing to uncover the microRNA (miRNA)-mediated defense mechanisms. Results: We identified colonization of F. oxysporum in A. macrocephala roots on day 6. Nine sRNA samples were sequenced to examine the dynamic changes in miRNA expression in A. macrocephala infected by F. oxysporum at 0, 6, and 12 days after inoculation. Furthermore, we using degradome sequencing and quantitative real-time PCR (qRT-PCR), validated four miRNA/target regulatory units involved in A. macrocephala-F. oxysporum interactions. Discussion: This study provides new insights into the molecular mechanisms underlying A. macrocephala's early defense against F. oxysporum infection, suggesting directions for enhancing resistance against this pathogen.

Comparison of six Z-score formulas based on echocardiography for coronary artery lesions in Kawasaki disease.

GOAL: Kawasaki disease (KD) patients are at risk of developing the serious complication of coronary artery dilation (CAD). To diagnose CAD caused by KD, various Z-Score formulas are used worldwide. This paper aims to evaluate the differences and inclusiveness among the six most commonly used Z-Score formulas in diagnosing CAD in Suzhou, China. Additionally, the study seeks to compare the differences in CAD diagnosis among different high-risk factor groups. By doing so, this research provides a valuable reference for accurately diagnosing CAD in KD patients. METHOD: This paper presents a retrospective analysis of 1509 patients diagnosed with KD at the Children's Hospital of Soochow University between January 2018 and December 2020. We collected the patients' clinical and echocardiographic data and used six Z-Score formulas (Kobayashi et al., de Zorzi et al., Kurotobi et al., McCrindle et al., Olivieri et al., and Dallaire et al.) to diagnose the degree of CAD in different segments. We then compared the diagnostic differences and inclusiveness of these formulas, especially the diagnostic differences in medium to giant CAA. To achieve this, we divided the patients into groups based on their age (≤12 months, 13-30 months, and > 30 months) and fever duration (≤5 days, 6-7 days, 8-9 days, and ≥ 10 days). Using the McNemar test and the Kappa test, we compared the differences and the consistencies of CDA diagnosis among the six Z-Score formulas. Moreover, we used the Friedman test and Chi-square segmentation formula to compare the differences in age and number of fever duration between groups and to compare each Z-Score formula pair within the group. RESULTS: Except for the LMCA segment, where there were no statistically significant differences between de Zorzi formula and McCrindle formula, the Z-score formulas showed statistically significant differences in the degree of CAD diagnosis across all other segments. Inclusiveness assessment revealed that Kobayashi formula and Dallaire formula showed significantly higher rates of dilatation (6.58% and 5.32%), or of small aneurysms (6.52% and 4.52%) compared to other formulas (1.0%-1.73%). Medium aneurysms were also more likely to be identified with Kobayashi and Dallaire formulas (0.8% and 0.8%) compared to the remaining formulas (0.13-0.40%). There are significant differences in the diagnoses of medium to giant CAA made by these six formulas in LAD and RCA. The longer the duration of fever and the younger the age, the higher the diagnosis rates of CAD and CAA. There were no statistically significant differences between de Zorzi formula and McCrindle formula, de Zorzi formula and Oliveri formula, and Kurotobi formula and Dallaire formula within the four groups based on the duration of fever. Similarly, there were no statistically significant differences between Kobayashi formula and Dallaire formula, and between de Zorzi formula and Oliveri formula in the age groups of ≤12 months and 13-30 months. CONCLUSION: There are diagnostic differences among these six Z-score formulas, considering the aforementioned statistics. Kobayashi formula and Dallaire formula are more inclusive, and less likely to under-diagnose significant CAD. They perform evenly for dilatation only, for small aneurysms and the median size aneurysms, and that is for segments of LMCA, LAD and RCA. In addition, McCrindle formula joins the "inclusive" pack for LAD and RCA in the matter of CAD. The younger the age of the patients and the longer the duration of fever, the higher the diagnosis rates of CAD and CAA. Furthermore, the younger the age of the patients and the shorter the duration of fever, the greater the differences between the various formulas.

Plasma proteomic profiling reveals that SERPINE1 is a potential biomarker associated with coronary artery lesions in Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is the most common cause of acquired heart disease in childhood. Coronary artery lesions (CALs) are serious complications of KD that can result in stenosis and thrombosis, but the specific underlying pathogenic mechanisms have not been elucidated. Therefore, exploring biomarkers to help predict early CALs is urgently needed for clinical treatment. METHODS: Patients were recruited from three independent cohorts. In the discovery cohort, Data-Independent Acquisition Mass Spectrometry (DIA-MS) was performed to screen plasma proteins from healthy controls (HCs), KD patients prior to intravenous immunoglobulin (IVIG) treatment, and KD patients post-IVIG treatment. KD patients were further divided into KD patients without CALs (nCAL) and with CALs (CALs) groups. Bioinformatic analysis was carried out for the differentially expressed proteins (DEPs) and hub proteins. Candidate proteins were quantified by enzyme-linked immunosorbent assay (ELISA) in the validation cohort 1 and 2. Furthermore, candida albicans cell wall extract (CAWS)-induced KD vasculitis mice and cell models were established to investigate the expression of biomarkers identified in the aforementioned clinical cohort. RESULTS: According to the quantitative proteomics analysis, SERPINE1 was significantly increased in KD patients with CALs. Receiver operating characteristic curves (ROC) revealed that plasma SERPINE1 exhibited greater ability in predicting CALs (AUC = 0.824, P < 0.0001). After IVIG treatment, the concentrations of SERPINE1 in the nCALs group significantly decreased. However, the concentration of SERPINE1 remained persistently elevated in the CALs group. Moreover, the expression of SERPINE1 was significantly upregulated in the heart tissue of KD mice, KD plasma, or tumor necrosis factor-α (TNF-α)-stimulated human coronary artery endothelial cells (HCAECs). CONCLUSIONS: Overall, our results suggest that the plasma concentration of SERPINE1 might serve as a new potential predictive biomarker for CALs in KD patients.

Prediction nomogram for coronary artery aneurysms at one month in Kawasaki disease.

BACKGROUND: Coronary status at one month after Kawasaki disease (KD) onset had a great significance. The present study aimed to establish a prediction model for coronary artery aneurysms (CAA) at one month in children with KD. METHODS: Patients with a diagnosis of KD between May 2017 and Dec 2018 were enrolled as the development cohort to build a prediction model. The model was validated by internal and external validation. Patients between Jan 2019 and Dec 2019 were enrolled as the validation cohort. The adaptive least absolute shrinkage and selection operator (LASSO) was used to select the possible predictors. Receiving operating characteristic curve (ROC), calibration plots, and decision curve analysis (DCA) were used to evaluate the performance of the model. The performance of the Son score was also assessed. RESULTS: LASSO regression demonstrated that age, sex, and CALs in the acute stage were predictors for CAA at one month. The area under the ROC (AUC) was 0.946 (95% confidence interval: 0.911-0.980) with a sensitivity of 92.5% and a specificity of 90.5%. The calibration curve and the DCA showed a favorable diagnostic performance. The internal and external validation proved the reliability of the prediction model. The AUC of our model and the Son score were 0.941 and 0.860, respectively (P < 0.001). CONCLUSION: Our prediction model for CAA at one month after disease onset in KD had an excellent predictive utility.

Bioinformatics analysis and identification of hub genes of neutrophils in Kawasaki disease: a pivotal study.

BACKGROUND: Kawasaki disease (KD) is considered the main contributor to acquired heart diseases in developed countries. However, the precise pathogenesis of KD remains unclear. Neutrophils play roles in KD. This study aimed to select hub genes in neutrophils in acute KD. METHODS: mRNA microarray of neutrophils from four acute KD patients and three healthy controls was performed to screen differentially expressed mRNAs (DE-mRNAs). DE-mRNAs were analyzed and predicted by Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways, and protein-protein interaction networks. Real time-PCR was finally conducted to confirm the reliability and validity of the expression level of DE-mRNAs from blood samples of healthy controls and KD patients in both acute and convalescent stage. RESULTS: A total of 1950 DE-mRNAs including 1287 upregulated and 663 downregulated mRNAs were identified. GO and KEGG analyses revealed the DE-mRNAs were mainly enriched in the regulation of transcription from RNA polymerase II promoter, apoptotic process, intracellular signal transduction, protein phosphorylation, protein transport, metabolic pathways, carbon metabolism, lysosome, apoptosis, pyrimidine metabolism, alzheimer disease, prion disease, sphingolipid metabolism, huntington disease, glucagon signaling pathway, non-alcoholic fatty liver disease, pyruvate metabolism, sphingolipid signaling pathway, and peroxisome. Twenty hub DE-mRNAs were selected including GAPDH, GNB2L1, PTPRC, GART, HIST2H2AC, ACTG1, H2AFX, CREB1, ATP5A1, ENO1, RAC2, PKM, BCL2L1, ATP5B, MRPL13, SDHA, TLR4, RUVBL2, TXNRD1, and ITGAM. The real-time PCR results showed that BCL2L1 and ITGAM mRNA were upregulated in acute KD and were normalized in the convalescent stage. CONCLUSIONS: These findings may improve our understanding of neutrophils in KD. Key Points • Neutrophilic BCL2L1 and ITGAM mRNA were first reported to be correlated with the pathogenic mechanism of KD.

Linear ubiquitination improves NFAT1 protein stability and facilitates NFAT1 signalling in Kawasaki disease.

NFAT1 is known for its roles in T cell development and activation. So far, the phosphorylation of NFAT1 has been extensively studied, but the other post-translational modifications of NFAT1 remain largely unknown. In this study, we reported that NFAT1 is a linearly ubiquitinated substrate of linear ubiquitin chain assembly complex (LUBAC). LUBAC promoted NFAT1 linear ubiquitination, which in turn inhibited K48-linked polyubiquitination of NFAT1 and therefore increased NFAT1 protein stability. Interestingly, the linear ubiquitination levels of NFAT1 in patients with the Kawasaki disease were upregulated. Further studies demonstrated that the patients with the Kawasaki disease had increased mRNA levels of HOIL-1L. These findings revealed a linearly ubiquitinated substrate of LUBAC and an important biological function of NFAT1 linear ubiquitination in the Kawasaki disease and therefore may provide a novel strategy for the treatment of the Kawasaki disease.

Biogenesis, Trafficking, and Function of Small RNAs in Plants.

Small RNAs (sRNAs) encoded by plant genomes have received widespread attention because they can affect multiple biological processes. Different sRNAs that are synthesized in plant cells can move throughout the plants, transport to plant pathogens via extracellular vesicles (EVs), and transfer to mammals via food. Small RNAs function at the target sites through DNA methylation, RNA interference, and translational repression. In this article, we reviewed the systematic processes of sRNA biogenesis, trafficking, and the underlying mechanisms of its functions.

Diameters of phloem sieve elements can predict stem growth rates of woody plants.

Understanding forest dynamics is crucial to addressing climate change and reforestation challenges. Plant anatomy can help predict growth rates of woody plants, contributing key information on forest dynamics. Although features of the water-transport system (xylem) have long been used to predict plant growth, the potential contribution of carbon-transporting tissue (phloem) remains virtually unexplored. Here, we use data from 347 woody plant species to investigate whether species-specific stem diameter growth rates can be predicted by the diameter of both the xylem and phloem conducting cells when corrected for phylogenetic relatedness. We found positive correlations between growth rate, phloem sieve element diameter and xylem vessel diameter in liana species sampled in the field. Moreover, we obtained similar results for data extracted from the Xylem Database, an online repository of functional, anatomical and image data for woody plant species. Information from this database confirmed the correlation of sieve element diameter and growth rate across woody plants of various growth forms. Furthermore, we used data subsets to explore potential influences of biomes, growth forms and botanical family association. Subsequently, we combined anatomical and geoclimatic data to train an artificial neural network to predict growth rates. Our results demonstrate that sugar transport architecture is associated with growth rate to a similar degree as water-transport architecture. Furthermore, our results illustrate the potential value of artificial neural networks for modeling plant growth under future climatic scenarios.