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Additional file 1.

Two novel acylated steroidal sapogenins, 3��-acetoxy-1��, 2��, 4��, 5��, 7��-pentahydroxy-spirost-25(27)-en-6-one (1) and (25S)-3��-acetoxy-1��, 2��, 4��, 5��, 7��-pentahydroxyspirostan-6-one (2), together with two known steroidal sapogenins (3 and 4), were isolated from Rohdea chinensis rhizomes. Their structures were elucidated by nuclear magnetic resonance (NMR) and mass spectrometry (MS) data. In addition, the antifungal activities of the isolated compounds against Penicillium digitatum and Rhizopus stolonifera were evaluated. Compound 2 significantly inhibited R. stolonifera growth, which was comparable to the positive control (sodium benzoate and carbendazim). Compound 4 showed the highest potency to inhibit P. digitatum growth compared to other compounds.

Importance Corticosteroids are widely used in pediatric cardiac surgery to blunt systemic inflammatory response and to reduce complications; nevertheless, their clinical efficacy is uncertain. Objective To determine whether intraoperative administration of dexamethasone is more effective than placebo for reducing major complications and mortality during pediatric cardiac surgery. Design, Setting, and Participants The Intraoperative Dexamethasone in Pediatric Cardiac Surgery was an investigator-initiated, double-blind, multicenter randomized trial that involved 4 centers in China, Brazil, and Russia. A total of 394 infants younger than 12 months, undergoing cardiac surgery with cardiopulmonary bypass were enrolled from December 2015 to October 2018, with follow-up completed in November 2018. Interventions The dexamethasone group (n = 194) received 1 mg/kg of dexamethasone; the control group (n = 200) received an equivolume of 0.9% sodium chloride intravenously after anesthesia induction. Main Outcomes and Measures The primary end point was a composite of death, nonfatal myocardial infarction, need for extracorporeal membrane oxygenation, need for cardiopulmonary resuscitation, acute kidney injury, prolonged mechanical ventilation, or neurological complications within 30 days after surgery. There were 17 secondary end points, including the individual components of the primary end point, and duration of mechanical ventilation, inotropic index, intensive care unit stay, readmission to intensive care unit, and length of hospitalization. Results All of the 394 patients randomized (median age, 6 months; 47.2% boys) completed the trial. The primary end point occurred in 74 patients (38.1%) in the dexamethasone group vs 91 patients (45.5%) in the control group (absolute risk reduction, 7.4%; 95% CI, −0.8% to 15.3%; hazard ratio, 0.82; 95% CI, 0.60 to 1.10;P = .20). Of the 17 prespecified secondary end points, none showed a statistically significant difference between groups. Infections occurred in 4 patients (2.0%) in the dexamethasone group vs 3 patients (1.5%) in the control group. Conclusions and Relevance Among infants younger than 12 months undergoing cardiac surgery with cardiopulmonary bypass, intraoperative administration of dexamethasone, compared with placebo, did not significantly reduce major complications and mortality at 30 days. However, the study may have been underpowered to detect a clinically important difference. Trial Registration ClinicalTrials.gov Identifier:NCT02615262

Additional file 7: Table S6. Annotations produced by DAVID for the transcriptionally changed genes.

Additional file 1: Table S1. Number of protein-protein interactions and participating unique proteins from three databases.

Additional file 6: Table S5. Annotations produced by the GO enrichment analysis tool for the transcriptionally changed genes.

Additional file 2: Table S2. Functional association evidence and computing methods.

Additional file 1: Figure S1. The effect of p47phox deficiency on the locomotor, spontaneous exploratory, and anxiety of APP/PS1 mice. The locomotion and spontaneous exploratory activity of mice aged 9 (a, b) and 12 (g, h) months was evaluated on Rotarod and open field tests, respectively. The anxiety of mice aged 9 months (c, d) and 12 months (i, j) was examined in open field and an elevated plus maze. Representative traces of a mouse’s movements during the open field test (e, k) and the elevated plus maze (f, l) are shown. Figure S2. p47phox deficiency does not affect APP levels in APP/PS1 mice. Representative Western blots showing APP expression in the hippocampus and the cortex of WT, APP/PS1, and APP/PS1-Ncf1−/− mice aged 9 months (a) and 12 months (c). b, d Quantification of immunoreactivity of Western blots, normalized against GAPDH. Figure S3. p47phox deficiency attenuates tau hyperphosphorylation in the cortex of APP/PS1 mice and ICV-STZ mice. Representative Western blots showing tau phosphorylation at S199, T205, S396, and S404 in the cortex of WT, APP/PS1, Ncf1−/−, and APP/PS1-Ncf1−/− mice aged 9 months (a) and 12 months (c), and of WT and Ncf1−/− mice receiving ICV injection of STZ or saline at the age of 6 months (e). (b, d, f) Quantifications of the immunoreactivity of Western blots are shown. Figure S4. p47phox deficiency attenuates tau aggregation and NTs in the hippocampus and the cortex of APP/PS1 mice. (a) Representative immunofluorescence staining showing the decreased tau aggregation and NTs in APP/PS1-Ncf1−/− mice aged 12 months, compared with age-matched APP/PS1 mice. Quantification of the fluorescence of AT8 is shown. Figure S5. p47phox deficiency attenuates NP tau in the hippocampus and the cortex of APP/PS1 mice. Representative immunofluorescence staining of AT8 and thioflavin-S (Thio-S) showing the decreased NP tau in APP/PS1-Ncf1−/− mice aged 12 months, compared with age-matched APP/PS1 mice. Figure S6. The expression of NOX subunits (p47phox, p67phox, and NOX2/gp91phox) in APP/PS1 mice. Representative Western blots showing p47phox, p67phox, and gp91phox expression in the brain of WT and APP/PS1 mice at the age of 9 months (a) and 12 months (c). (b, d) Quantifications of the immunoreactivity of Western bolts are shown. Figure S7. p47phox deficiency inhibits the activation of astrocytes in APP/PS1 mice. (a) Representative immunofluorescence staining showing the decreased expression of GFAP in APP/PS1-Ncf1−/− mice aged 9 months and 12 months, compared with age-matched APP/PS1 mice. (b) Quantification of the fluorescence of GFAP is shown. Figure S8. p47phox deficiency inhibits the activation of microglia in APP/PS1 mice. (a) Representative immunofluorescence staining showing the decreased expression of Iba1 in APP/PS1-Ncf1−/− mice aged 12 months, compared with age-matched APP/PS1 mice. (b) Quantification of the fluorescence of Iba1 is shown. Figure S9. p47phox deficiency inhibits high glucose-induced activation of primary astrocytes. Primary cultures of astrocytes from WT and Ncf1−/− newborn mice were treated with DMEM with or without high glucose (75 mM and 150 mM) for 24 h and 48 h. (a) Representative Western blots showing the expression of GFAP. (b, c) Quantification of the immunoreactivity of Western blots is shown.

Additional file 3: Table S3. Assessment of feature quality.

Additional file 8: Table S7. Annotations produced by FIC/GSLA for the transcriptionally changed genes.

Additional file 4: Figure S1. Receiver operating characteristic (ROC) curves of 36 feature values. Features with areas under the curve (AUC) above 0.6 were selected for use in the SVM model to predict functional interactions between genes.