Untargeted lipidomics of bronchopulmonary dysplasia induced by hyperoxia exposure in rats.

Background: Bronchopulmonary dysplasia (BPD), characterized by impaired lung development, remains a leading cause of morbidity and mortality in premature infants. The synthesis and metabolism of lipids play a critical role in normal lung development, such as dipalmitoylphosphatidylcholine, a key component of pulmonary surfactant (PS). Therefore, we conducted a lipidomics study of rat lung tissue to explore the changes of pulmonary lipid composition in the progression of BPD disease. Methods: In this study, we exposed neonatal Sprague-Dawley (SD) rats to hyperoxia for 14 days. After hyperoxia exposure, the lung tissues of rats were analyzed pathologically, and untargeted lipidomics was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Hematoxylin-eosin (H&E) staining showed that the alveoli enlarged, the number of alveoli decreased and the pulmonary surfactant-associated protein D (SFTPD) decreased in hyperoxia-exposed rats. A total of 620 pulmonary lipids were detected by LC-MS/MS, covering 27 lipid categories. The most common lipids were triacylglycerol (TAG), followed by phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Conclusions: Compared with those rats exposed to normoxic conditions, the lipid levels in the lungs of rats exposed to hyperoxia for 14 days generally decreased, with the levels of TAG and PC decreasing most significantly. In short, our results provide a clue for finding therapeutic targets and biomarkers of a BPD rat model lung liposome.

PC (16:0/14:0) ameliorates hyperoxia-induced bronchopulmonary dysplasia by upregulating claudin-1 and promoting alveolar type II cell repair.

Bronchopulmonary dysplasia (BPD) remains a significant challenge in neonatal care, the pathogenesis of which potentially involves altered lipid metabolism. Given the critical role of lipids in lung development and the injury response, we hypothesized that specific lipid species could serve as therapeutic agents in BPD. This study aimed to investigate the role of the lipid Phosphatidylcholine (PC) (16:0/14:0) in modulating BPD pathology and to elucidate its underlying mechanisms of action. Our approach integrated in vitro and in vivo methodologies to assess the effects of PC (16:0/14:0) on the histopathology, cellular proliferation, apoptosis, and molecular markers in lung tissue. In a hyperoxia-induced BPD rat model, we observed a reduction in alveolar number and an enlargement in alveolar size, which were ameliorated by PC (16:0/14:0) treatment. Correspondingly, in BPD cell models, PC (16:0/14:0) intervention led to increased cell viability, enhanced proliferation, reduced apoptosis, and elevated surfactant protein C (SPC) expression. RNA sequencing revealed significant gene expression differences between BPD and PC (16:0/14:0) treated groups, with a particular focus on Cldn1 (encoding claudin 1), which was significantly enriched in our analysis. Our findings suggest that PC (16:0/14:0) might protect against hyperoxia-induced alveolar type II cell damage by upregulating CLDN1 expression, potentially serving as a novel therapeutic target for BPD. This study not only advances our understanding of the role of lipids in BPD pathogenesis, but also highlights the significance of PC (16:0/14:0) in the prevention and treatment of BPD, offering new avenues for future research and therapeutic development.

Human milk exosome-derived circDNAJB6 improves bronchopulmonary dysplasia model by promoting DNAJB6 gene transcription.

To verify the protective effect of circDNAJB6 on Bronchopulmonary dysplasia (BPD) cell and animal models and to explore the possible mechanism of its protective effect. The function of circDNAJB6 was investigated at the cell and animal levels. Nuclear and Cytoplasmic RNA extraction kits and fluorescence in situ hybridization (FISH) were used to explore the distribution of circDNAJB6 in cells, and the potential mechanism of circDNAJB6 was verified by q-PCR, luciferase assays and rescue experiments.CircDNAJB6 is abundant in breast milk exosomes. Overexpression of circDNAJB6 can ameliorate damage in BPD models caused by hyperoxia exposure in vivo and in vitro. Mechanistically, circDNAJB6 can target the downstream DNAJB6 gene and promote the transcription of DNAJB6, exertive a protective effect on the experimental BPD model. Our results showed that circDNAJB6 alleviated damage and inhibited the proliferation of alveolar epithelial cells in the BPD model by promoting transcription of parent gene DNAJB6. Human milk exosome-derived circDNAJB6 provides new directions for preventing and treating BPD.

The role of polypeptide PDTLN1 in suppression of PI3K/AKT signaling causes cardiogenetic disorders in vitro and in vivo.

AIMS: A new polypeptide, PDTLN1, derived from the human Talin-1 protein, which is highly expressed in both myocardial tissue and maternal peripheral blood of aborted fetuses with congenital heart disease (CHD). However, its role in cardiac developmental disorders has not been disclosed till now. In the present study, we aim to assess the functions of PDTLN1 in heart development of zebrafish and cellular viability, proliferation, and apoptosis of P19 cells. MAIN METHODS: Cellular viability was assessed by Cell Counting Kit-8, the EdU Kit was used to evaluate cellular proliferation, and apoptosic rate of P19 was examined using FITC Annexin-V staining followed by flow cytometry. The zebrafish embryos were divided into three groups: PEP group and NC group were microinjected with polypeptides, WT group without any intervention. The protein expression of PI3K/AKT were evaluated by western blotting. KEY FINDINGS: PDTLN1 could suppress the proliferation, and facilitate apoptosis. PDTLN1 caused abnormal heart development of zebrafish embryos and the PDTLN1 (50 µM)-injected group showed an aberrant expression pattern of vmhc, amhc and cmlc2. Compared to the CTL group and SC79 group of P19 cells, the PDTLN1 group had a lower phosphorylated PI3K/AKT proteins level, decreased cellular viability and lower proliferation activity. SIGNIFICANCE: PDTLN1 caused cardiac developmental defects in zebrafish, inhibited cellular viability, proliferation, and promoted apoptosis of P19 cells via suppressing the PI3K/AKT signaling pathway. Our findings provide a fresh perspective on the functional mechanism of human-derived peptides and may promote novel diagnostic biomarkers detection and therapeutic targets in CHD.

Differential Expression Profiles and Functional Prediction of circRNAs in Necrotizing Enterocolitis.

Circular RNAs (circRNAs), a novel type of noncoding RNAs, have been demonstrated to behave as microRNA (miRNA) sponges to exert their effects during pathological processes of diseases. However, the roles of circRNAs have not been explored in necrotizing enterocolitis (NEC). This study sought to identify differentially expressed circRNAs and predict their potential biological functions in NEC. circRNA expression profiles in terminal ileum from newborn rats with NEC and normal controls were explored using next-generation sequencing. In the NEC group, 53 circRNAs were significantly differentially expressed, including 9 upregulated and 44 downregulated. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted, and circRNA-miRNA interaction networks were generated to predict the potential roles of circRNAs in NEC progression. Further investigation revealed that most circRNAs include miRNA binding sites and that some are implicated in NEC development. In conclusion, this study's findings demonstrate that differentially expressed circRNAs are involved in NEC development via their interactions with miRNAs, making them prospective targets for NEC diagnosis and treatment.

Circular RNA hsa_circ_105039 promotes cardiomyocyte differentiation by sponging miR­17 to regulate cyclinD2 expression.

Previously it was found that hsa_circ_105039 was underexpressed in the heart tissue of patients with congenital heart disease (CHD). However, the function and mechanism of hsa_circ_105039 in CHD are unclear. In the present study, induced pluripotent stem (iPS) cells were differentiated into cardiomyocytes using 1% dimethyl sulfoxide (DMSO). Cell differentiation, viability, migration and apoptosis were measured before and following hsa_circ_105039 knockdown or overexpression. The results indicated that hsa_circ_105039 overexpression promoted cell differentiation, viability and migration; whereas apoptosis was simultaneously repressed. A luciferase reporter assay verified that hsa_circ_105039 acted as a sponge for microRNA (miR)­17 and that cyclinD2 was a direct target of miR­17. Furthermore, differentiation­related genes and proteins were analyzed by reverse transcription­quantitative PCR and western blotting, respectively. The results showed that hsa_circ_105039 could also upregulate the expression of differentiation­related genes and proteins, including natriuretic peptide A, cardiac troponin I, GATA­binding protein 4 and homobox transcription factor, in iPS cells. The results suggested that hsa_circ_105039 exerted a protective effect by promoting miR­17/cyclinD2 in DMSO­induced iPS cardiomyocytes, which indicated that hsa_circ_105039 is a potential key molecule for the diagnosis of CHD.

Lipidomic Profiling of Human Milk Derived Exosomes and Their Emerging Roles in the Prevention of Necrotizing Enterocolitis.

SCOPE: Human milk can prevent the development of necrotizing enterocolitis (NEC). Human milk is rich in cargo-carrying exosomes that participate in intercellular communication. This study investigated the effects of term and preterm human milk-derived exosomes, and elucidated their lipid expression profiles. METHODS AND RESULTS: Milk from healthy mothers is collected who have delivered full-term or preterm infants, and exosomes are isolated and quantified. Administration of term and preterm milk exosomes significantly enhances epithelial proliferation and migration in vitro, and ameliorates the severity of NEC in vivo. A total of 395 lipids are identified in term and preterm human milk-derived exosomes. Bioinformatics analysis and western blotting reveal that top 50 lipids regulate intestinal epithelial cell function via the Extracellular-Signal-Regulated Kinase/Mitogen Activated Protein Kinase (ERK/MAPK) pathway. CONCLUSION: This study reveals for the first time the lipidomic complexities in exosomes derived from preterm and term milk. The results provide novel mechanistic insight on how human milk prevents the development of NEC.

[Diurnal changes in greenhouse gases at water-air interface of Xiangxi River in autumn and their influencing factors].

With the closed chamber and gas chromatography method, a 24-hour continuous monitoring was carried out to understand the greenhouse gases fluxes across the water-air interface of the Xiangxi River Bay, the Three-Gorges Reservoir in Autumn. Results indicated that the fluxes of CO2, CH4 and N2O across the water-air interface showed an obvious diurnal variation. The absorption and emission process of CH4 showed strong diurnal variation during the experimental period, reaching the highest emission at 1 am, whereas CO2 and N2O were emitted all day. The fluxes of CO2 ranged from 20.1-97.5 mg x (m2 x h)(-1) at day and 32.7-42.5 mg x (m2 x h)(-1) at night, the fluxes of N2O ranged from 18.4-133.7 microg x (m2 x h)(-1) at day and 42.1-102.6 microg x (m2 x h)(-1) at night. The fluxes of CO2 had positive correlation with wind speed and negative correlation with pH. The fluxes of N2O had positive correlation with pH.

Non-microcystin producing Microcystis wesenbergii (Komárek) Komárek (Cyanobacteria) representing a main waterbloom-forming species in Chinese waters.

It is well known that several morphospecies of Microcystis, such as Microcystis aeruginosa (Kützing) Lemmermann and Microcystis viridis (A. Brown) Lemmermann can produce hepatotoxic microcystins. However, previous studies gave contradictory conclusions about microcystin production of Microcystis wesenbergii (Komárek) Komárek. In the present study, ten Microcystis morphospecies were identified in waterblooms of seven Chinese waterbodies, and Microcystis wesenbergii was shown as the dominant species in these waters. More than 250 single colonies of M. wesenbergii were chosen, under morphological identification, to examine whether M. wesenbergii produce hepatotoxic microcystin by using multiplex PCR for molecular detection of a region (mcyA) of microcystin synthesis genes, and chemical analyses of microcystin content by ELISA and HPLC for 21 isolated strains of M. wesenbergii from these waters were also performed. Both molecular and chemical methods demonstrated that M. wesenbergii from Chinese waters did not produce microcystin.

[Adaptability of Moina affinis (Crustacea: Cladocera: Moinidae) to seawater salinity].

By the methods of experimental ecology, this paper studied the effects of different salinity (0, 1, 2, 3, 4, 5) on the survival, growth, and reproduction of Moina affinis (Crustacea: Cladocera: Moinidae) at 25 degrees C +/- 0.5 degrees C under laboratory conditions, aimed to know the adaptability of freshwater cladocerans to seawater salinity. The results indicated that when the salinity increased from 0 to 5, the mean lifespan of M. affinis was 16.8 +/- 1.3, 17.8 +/- 3.5, 14.2 +/- 5.7, 13.0 +/- 1.6, 9.6 +/- 1.5 and 6.6 +/- 1.8 days, intrinsic increase rate (rm) was 0.91 +/- 0.01, 0.96 +/- 0.01, 0.86 +/- 0.10, 0.86 +/- 0.05, 0.49 +/- 0.18 and 0.24 +/- 0.06 d (-1) mean eggs production per clutch was 34.5 +/- 3.7, 34.2 +/- 3.9, 27.5 +/- 7.1, 34.6 +/- 3.9, 12.3 +/- 5.0 and 9.1 +/- 2.1 ind., and life fecundity was 410 +/- 32, 445 +/- 84, 250 +/- 106, 294 +/- 47, 59 +/- 38 and 24 +/- 6 ind., respectively. There was a significant difference in mean lifespan, intrinsic increase rate, and mean eggs production per clutch between treatments salinity 0, 1, 2 and 3 and treatments salinity 4 and 5, and in life fecundity between treatments salinity 0 and 1 and treatments salinity 2, 3, 4 and 5. The body length and daily growth rate was lower in control than in other treatments. It was suggested that salinity 5 was the maximum threshold salinity for the survival and reproduction of M. affinis, but after a short period of acclimatization in diluted seawater, the maximum threshold could reach 6. 5.