Concentration and composition of odd-chain fatty acids in phospholipids and triacylglycerols in Chinese human milk throughout lactation.

Human milk represents the gold standard for infant nutrition, with approximately 50% of the energy in human milk derived from lipids. Odd-chain fatty acids (OCFAs) have been recognized as a category of bioactive milk fatty acids in recent research; however, limited data exist on OCFAs in human milk. This study collected human milk samples spanning the postpartum period from 0 to 400 days. Phospholipids containing OCFAs (PL-OCFAs) were determined in 486 human milk samples using hydrophilic liquid chromatography-electrospray ionization-triquadrupole-mass spectrometry. Triacylglycerols containing OCFAs (TAG-OCFAs) were analyzed in 296 human milk samples using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The average total concentration of PL-OCFA ranged from 30.89 ± 14.27 mg L-1 to 93.48 ± 36.55 mg L-1 during lactation, and the average total TAG-OCFA content ranged from 103.1 ± 147.15 mg L-1 to 965.41 ± 651.67 mg L-1. Despite the lower absolute concentration of PL-OCFA, its relative concentration (8.75%-11.75%) was significantly higher than that of TAG-OCFA (0.37%-1.85%) throughout lactation. PC-OCFA, SM-OCFA and PE-OCFA are major sub-classes of PL-OCFA. Furthermore, C17:0 was the major chain length in both PL-OCFA and TAG-OCFA, followed by C15:0. C17:1 was characteristic of TAG-OCFA, while long-chain fatty acids C19:0, C21:0 and C23:0 were characteristic of PL-OCFA. Our findings highlighted the importance of bioactive lipids in human milk, suggesting that OCFAs could be targeted in future studies in relation to the health and development of infants.

Corrigendum: Identification of ACKR4 as an immune checkpoint in pulmonary arterial hypertension.

[This corrects the article DOI: 10.3389/fimmu.2023.1153573.].

Identification of ACKR4 as an immune checkpoint in pulmonary arterial hypertension.

Objective: Inflammation is recognized as a contributor in the development of pulmonary arterial hypertension (PAH), and the recruitment and functional capacity of immune cells are well-orchestrated by chemokines and their receptors. This study is aimed at identification of critical chemokines in the progression of PAH via transcriptomic analysis. Methods: Differentially expressed genes (DEGs) from lungs of PAH patients were achieved compared to controls based on Gene Expression Omnibus (GEO) database. Gene set enrichment analysis (GSEA) was applied for functional annotation and pathway enrichement. The abundance of immune cells was estimated by the xCell algorithm. Weighted correlation network analysis (WGCNA) was used to construct a gene expression network, based on which a diagnostic model was generated to determine its accuracy to distinguish PAH from control subjects. Target genes were then validated in lung of hypoxia-induce pulmonary hypertension (PH) mouse model. Results: ACKR4 (atypical chemokine receptor 4) was downregulated in PAH lung tissues in multiple datasets. PAH relevant biological functions and pathways were enriched in patients with low-ACKR4 level according to GSEA enrichment analysis. Immuno-infiltration analysis revealed a negative correlation of activated dendritic cells, Th1 and macrophage infiltration with ACKR4 expression. Three gene modules were associated with PAH via WGCNA analysis, and a model for PAH diagnosis was generated using CXCL12, COL18A1 and TSHZ2, all of which correlated with ACKR4. The ACKR4 expression was also downregulated in lung tissues of our experimental PH mice compared to that of controls. Conclusions: The reduction of ACKR4 in lung tissues of human PAH based on transcriptomic data is consistent with the alteration observed in our rodent PH. The correlation with immune cell infiltration and functional annotation indicated that ACKR4 might serve as a protective immune checkpoint for PAH.

Corrigendum: The neutrophil elastase inhibitor, Sivelestat, attenuates acute lung injury in patients with cardiopulmonary bypass.

[This corrects the article DOI: 10.3389/fimmu.2023.1082830.].

The neutrophil elastase inhibitor, sivelestat, attenuates acute lung injury in patients with cardiopulmonary bypass.

Background: The sivelestat is a neutrophil elastase inhibitor thought to have an effect against acute lung injury (ALI) in patients after scheduled cardiac surgery. However, the beneficial effect of sivelestat in patients undergoing emergent cardiovascular surgery remains unclear. We aim to evaluate the effect of sivelestat on pulmonary protection in patients with ALI after emergent cardiovascular surgery. Methods: Firstly, a case-control study in 665 patients undergoing emergent cardiovascular surgery from January 1st, 2020 to October 26th, 2022 was performed. 52 patients who received sivelestat (0.2mg/kg/h for 3 days) and 613 age- and sex-matched controls. Secondly, a propensity-score matched cohort (sivelestat vs control: 50 vs 50) was performed in these 665 patients. The primary outcome was a composite of adverse outcomes, including 30-day mortality, ECMO, continuous renal replacement therapy (CRRT) and IABP, etc. The secondary outcome included pneumonia, ventricular arrhythmias and mechanical ventilation time, etc. Results: In propensity-matched patients, the 30-day mortality (16% vs 24%, P=0.32), stroke (2% vs 8%, P=0.17), ECMO(6% vs 10%, P=0.46), IABP(4% vs 8%, P=0.40) and CRRT(8% vs 20%, P=0.08) had no differences between sivelestat and control group; sivelestat could significantly decrease pneumonia (40% vs 62%, P=0.03), mechanical ventilation time (median: 96hours, IQR:72-120hours vs median:148hours, IQR:110-186hours, P<0.01), bilateral pulmonary infiltrates (P<0.01), oxygen index (P<0.01), interleukin-6(P=0.02), procalcitonin(P<0.01) and C-reactive protein(P<0.01). Conclusion: Administration of sivelestat might improve postoperative outcomes in patients with ALI after emergent cardiovascular surgery. Our results show that sivelestat may be considered to protect pulmonary function against inflammatory injury by CPB. Registration: http://www.chictr.org.cn/showproj.aspx?proj=166643, identifier ChiCTR2200059102.

The low-dose colchicine in patients after non-CABG cardiac surgery: a randomized controlled trial.

BACKGROUND: Recent high-quality trials have shown that the anti-inflammatory effects of colchicine reduce the risk of cardiovascular events in patients suffering post-myocardial infarction and chronic coronary disease. The effect of colchicine in patients undergoing non-coronary artery bypass grafting (non-CABG) with cardiopulmonary bypass remains unclear. We aim to evaluate the effect of colchicine on myocardial protection in patients who underwent non-CABG cardiac surgery. METHOD: Patients were randomly assigned to colchicine or placebo groups starting 72 h before scheduled cardiac surgery and for 5 days thereafter (0.5 mg daily).The primary outcome was the level of cardiac troponin T (cTnT) at postoperative 48 h. The secondary outcomes included troponin I (cTnI) and creatine kinase-MB (CK-MB), inflammatory biomarkers (procalcitonin and interleukin-6, etc.), and adverse events (30-day mortality, stroke, ECMO and IABP use, etc.). RESULTS: A total of 132 patients underwent non-CAGB cardiac surgery, 11were excluded because of diarrhea (n = 6) and long aortic cross-clamp time > 2 h (n = 5), 59 were assigned to the colchicine group and 62 to the placebo group. Compared with the placebo group, cTnT (median: 0.3 µg/L, IQR 0.2-0.4 µg/L vs. median: 0.4 µg/L, IQR 0.3-0.6 µg/L, P < 0.01), cardiac troponin I (median: 0.9 ng/ml, IQR 0.4-1.7 ng/ml vs. median: 1.3 ng/ml, IQR 0.6-2.3 ng/ml, P = 0.02), CK-MB (median: 1.9 ng/ml, IQR 0.7-3.2 ng/ml vs. median: 4.4 ng/ml, IQR 1.5-8.2 ng/ml, P < 0.01), and interleukin-6 (median: 73.5 pg/ml, IQR 49.6-125.8 pg/ml vs. median: 101 pg/ml, IQR 57.5-164.7 pg/ml, P = 0.048) were significantly reduced in colchicine group at postoperative 48 h. For safety evaluation, the colchicine (n = 65) significantly decreased post-pericardiotomy syndrome (3.08% vs. 17.7%, P < 0.01) and increased the rate of diarrhea (9.23% vs. 0, P = 0.01) compared with the placebo group (n = 62). No significant difference was observed in other adverse events between the two groups. CONCLUSION: A short perioperative course of low-dose colchicine was effective to attenuate the postoperative biomarkers of myocardial injury and inflammation, and to decrease the postoperative syndrome compared with the placebo. Trial registration ChiCTR2000040129. Registered 22nd Nov. 2020. This trial was registered before the first participant was enrolled. http://www.chictr.org.cn/showproj.aspx?proj=64370 .

Profiling of triacylglycerol composition in the breast milk of Chinese mothers at different lactation stages.

Triacylglycerol (TAG) is the primary constituent of human milk fat and plays a vital role in the healthy development of infants. But few studies reported the sophisticated profile of TAG molecular species in human breast milk and its temporal changes during a prolonged lactation period. An efficient ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) method was adopted to examine TAGs. A total of 128 TAGs in 296 human breast milk samples collected during postnatal 0 to 400 days were identified. The changes in the human milk TAG profile mainly took place in the early stages of lactation (postnatal 0-45 days), and the TAG profile became stable in mature milk after 200 days of lactation. Odd chain fatty acids (OC-FAs) may be important markers for identifying human breast milk of different lactation stages. This study could provide evidence for developing safe and efficacious human-milk substitutes for children without access to human breast milk.

Datinolides E-I, five new withanolides with anti-inflammatory activity from the leaves of Datura inoxia Mill.

Five new withanolides, datinolides E-I (1-5), and three known withanolides (6-8) were separated from Datura inoxia Mill. leaves, and datinolide E (1) was the first withanolide with C-27 connected to a nitrogen-containing group. Their structures were clarified by comprehensive spectroscopic analysis and comparison with literature. The anti-inflammatory of isolated compounds against RAW264.7 cells was investigated by the CCK8 assay.

Lactonase activity and status of paraoxonase 1 and oxidative stress in neonates of women with gestational diabetes mellitus.

BACKGROUND: The level and lactonase activity of paraoxonase 1 (PON1) and their association with PON1 genetic variants and oxidative stress are unclear in neonates of women with gestational diabetes mellitus (GDM). METHODS: This study included 362 neonates of women with GDM and 302 control neonates. The level, lactonase activity, normalized lactonase activity (NLA), and genetic polymorphisms of PON1, serum total oxidant status (TOS), total antioxidant capacity (TAC), and malondialdehyde (MDA) were analyzed. RESULTS: The neonates of the women with GDM had significantly higher levels, lactonase activity, and NLA of PON1, higher TOS, TAC, and MDA concentrations, and relatively higher oxidative stress index than those of the control neonates. The PON1 -108C → T variation decreased the lactonase activity, level, and NLA of PON1, while the PON1 192Q → R variation decreased the PON1 NLA in a genotype-dependent manner in the two groups. Multivariable regression analysis revealed the PON1 -108C/T or 192Q/R variation, apolipoprotein (apo)A1, or apoB as significant predictors of the level, lactonase activity, and NLA of PON1. CONCLUSIONS: The lactonase activity, level, and NLA of PON1 were increased in the neonates of women with GDM. The PON1 genetic variants, abnormalities in lipoproteins, and increased oxidative stress may be associated with these changes. IMPACT: This is the first study to report the elevated level, lactonase activity, and NLA of PON1 in the neonates of women with GDM. These neonates also exhibited increased oxidative stress and an adverse glycolipid metabolic profile. We further established that the -108C/T and/or 192Q/R genetic variants of the PON1 gene, abnormalities in lipoprotein metabolism, and/or increased oxidative stress had noticeable influences on the level and activities of PON1. Whether these changes potentially cause metabolic disorders later in life remains to be determined. Therefore, the neonates born to women with GDM require further clinical follow-ups.

Porous MOF with Highly Efficient Selectivity and Chemical Conversion for CO2.

A new Co(II)-based MOF, {[Co2(tzpa)(OH)(H2O)2]·DMF}n (1) (H3tzpa = 5-(4-(tetrazol-5-yl)phenyl)isophthalic acid), was constructed by employing a tetrazolyl-carboxyl ligand H3tzpa. 1 possesses 1D tubular channels that are decorated by µ3-OH groups, uncoordinated carboxylate O atoms, and open metal centers generated by the removal of coordinated water molecules, leading to high CO2 adsorption capacity and significantly selective capture for CO2 over CH4 and CO in the temperature range of 298-333 K. Moreover, 1 shows the chemical stability in acidic and basic aqueous solutions. Grand canonical Monte Carlo simulations identified multiple CO2-philic sites in 1. In addition, the activated 1 as the heterogeneous Lewis and Brønsted acid bifunctional catalyst facilitates the chemical fixation of CO2 coupling with epoxides into cyclic carbonates under ambient conditions.

[Investigation on rapid detection of lead by LIBS based on common spectrograph].

In the present paper, the lead concentrations of samples including glass, soldering tin and so on were determined by LIBS based on a Nd : YAG Q-switched pulse laser with wavelength 1 064 nm as an exciting source and CCD in common spectrograph as the detector. The pulse energy on the surface of samples is about 95 mJ and the pulse width is 12 ns. By the detection of different samples, the detection limit of lead in samples was found to be 0.007 4% and the maximum relative standard deviation of quantitative analysis was about 4.0% based on the LIBS system of the instruments all made in China. The quantitative analysis can be done in two or three minutes and will spend one minute finishing the process by software in the future. The results suggest that the accuracy of determination of lead meets the challenge of quantitative analysis and the CCD can displace the very expensive ICCD as detector. The feasibility and low cost of the method, which uses common spectrometer and CCD to realize the LIBS detection, is proved by the result and our investigation will be beneficial to the LIBS application.