Allogeneic haematopoietic stem cell transplantation might overcome the poor prognosis of adolescents and adult patients with T-lineage acute lymphoblastic leukaemia and CDKN2 deletion.

This study delves into the clinical implications of cyclin-dependent kinase inhibitor 2 (CDKN2) deletion in adult T-lineage acute lymphoblastic leukemia (T-ALL). Among 241 patients included in this study, 57 had CDKN2 deletion and 184 had CDKN2 wild-type (WT), and 165 underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 76 did not undergo allo-HSCT. CDKN2 deletion correlated with higher white blood cell count, more high-risk diseases, and complex karyotype. The 5-year overall survival (OS) was 36.8% and 58.2% (P < 0.001), 5-year disease-free survival (DFS) was 47.1% and 59.3% (P = 0.018), and 5-year cumulative incidence of relapse (CIR) was 33.7% and 22.3% (P = 0.019) in patients with CDKN2 deletion and WT, respectively. Multivariate analysis identified CDKN2 deletion as an independent adverse prognostic factor for OS (HR 2.11, P = 0.003). In the CDKN2 deletion subgroup, landmark analysis showed that the 5-year OS was 56.7% and 19% (P = 0.002) for patients who underwent allo-HSCT and those who did not, respectively. And multivariate analysis confirmed the beneficial role of allo-HSCT in OS (HR 0.23, P < 0.001). In conclusion, CDKN2 deletion was associated with a poor prognosis in adult T-ALL, and allo-HSCT might be beneficial for this population.

Influence of early childhood teachers' psychological contracts on teacher competency: Chain mediating role of job crafting and professional identity.

In response to the epochal demand for high-quality development in early childhood education in China, it is imperative and necessary to improve the competency level of early childhood educators. The study aims to investigate the relationship between psychological contracts and teacher competency, and to verify the mediating roles of job crafting and professional identity in the relationship between psychological contracts and teacher competency. This study employed validated measurement scales regarding psychological contracts, teachers' professional identity, job crafting, and teacher competency. Each of these scales has established internal consistency coefficients. Data were collected from 318 early childhood teachers in Sichuan, China. The results highlight the significant impact of psychological contracts on the prediction of teacher competency. It is worth mentioning that the psychological contracts, together with their distinct components such as normative responsibility and development responsibility, have a direct and favorable impact on teacher competency. This implies that developing the psychological contracts might be an effective technique for improving teacher competence. The individual mediation of job crafting and professional identity in the link between psychological contracts and teacher competency has been well-established. However, the combined or chain mediating influence of these factors provides a unique and valuable perspective on the phenomenon of job crafting leading to professional identity, which in turn impacts teacher competency. The study found that psychological contracts have a positive predictive effect on teacher competency, while job crafting and professional identity both have independent and chain mediating roles in the relationship between psychological contracts and teacher competency. Therefore, this study suggests a comprehensive enhancement of the psychological contracts level from aspects such as normative responsibility, interpersonal responsibility, and development responsibility. By stimulating job crafting and professional identity levels in both internal and external environments, we can improve the competency level of early childhood educators.

Incidence and Risk Factors for Retinopathy of Prematurity in a Tertiary Hospital in China.

Purpose: To investigate the incidence and risk factors for the retinopathy of prematurity (ROP) in the neonatal intensive care unit (NICU) of Obstetrics and Gynecology Hospital of Affiliated to Nanjing Medical University, China. Methods: This retrospective case-control study included 611 preterm infants with birth weight (BW)<1500 grams admitted to the Department of Neonatology, Obstetrics and Gynecology Hospital of Affiliated to Nanjing Medical University between January 2019 and December 2022. The incidence and risk factors for any stage and severe ROP were analyzed. Results: Within 611 infants, 245(40.1%) developed ROP; 160(26.2%) infants were stage 1, 54(8.8%) were stage 2, and 31(5.1%) were stage 3, no stage 4 and 5. Among them, 22(3.6%) infants needed treatment. Multivariate analysis showed a higher gestational age (GA) was protective, whereas twin birth and moderate-to-severe BPD increased the hazard of any stage ROP; higher BW and male gender were significant risk factors for severe ROP. Conclusion: Compared to other tertiary hospitals, the incidence of any stage ROP in our NICU was higher, but the rate of ROP needed treatment was lower. A higher GA was protective, whereas twin birth and moderate-to-severe BPD increased the hazard of any stage ROP; higher BW was protective, whereas male gender were risk factors for the development of severe ROP.

The casein-derived peptide YFYPEL alleviates intestinal epithelial cell dysfunction associated with NEC by regulating the PI3K/AKT signaling pathway.

Necrotizing enterocolitis (NEC) is a life-threatening risk to the health of neonates, but thus far, there is no very effective treatment. Although many studies have confirmed the therapeutic role of peptides in diseases, the effect of peptides in NEC remains poorly understood. This study investigated the role of casein-derived peptide YFYPEL in NEC cells and animal models. We synthesized YFYPEL and analysed its protective effects on NEC both in vitro and in vivo. YFYPEL integration in the intestine increased rat survival and clinical conditions, lowered the incidence of NEC, alleviated bowel inflammation, and enhanced intestinal cell migration. Furthermore, YFYPEL significantly decreased interleukin 6 expression and increased intestinal epithelial cell migration. Moreover, YFYPEL alleviated intestinal epithelial cell dysfunction through the PI3K/AKT pathway, as demonstrated by western blotting and bioinformatics analysis. A selective PI3K activator reversed the protective effect of YFYPEL on lipopolysaccharide-stimulated intestinal epithelial cells. Our study showed that YFYPEL reduced inflammatory cytokine expression and enhanced migration by regulating the PI3K/AKT pathway. The use of YFYPEL may thus develop into a novel modality in NEC treatment.

Survey on human milk feeding and enteral feeding practices for very-low-birth-weight infants in NICUs in China Neonatal Network.

BACKGROUND: The breastfeeding rate in China is lower than that in many other countries and the extent of adoption of the "Feeding Recommendations for Preterm Infants and Low Birth Weight Infants" guideline in NICUs remains unclear. METHOD: A web-based survey about the current status of human milk feeding and enteral feeding practices at NICUs was sent to all China Neonatal Network's cooperation units on September 7, 2021, and the respondents were given a month to send their responses. RESULTS: All sixty NICUs responded to the survey, the reply rate was 100%. All units encouraged breastfeeding and provided regular breastfeeding education. Thirty-six units (60.0%) had a dedicated breastfeeding/pumping room, 55 (91.7%) provided kangaroo care, 20 (33.3%) had family rooms, and 33 (55.0%) routinely provided family integrated care. Twenty hospitals (33.3%) had their own human milk banks, and only 13 (21.7%) used donor human milk. Eight units (13.3%) did not have written standard nutrition management guidelines for infants with body weight < 1500 g. Most units initiated minimal enteral nutrition with mother's milk for infants with birth weight ˂1500 g within 24 h after birth. Fifty NICUs (83.3%) increased the volume of enteral feeding at 10-20 ml/kg daily. Thirty-one NICUs (51.7%) assessed gastric residual content before every feeding session. Forty-one NICUs (68.3%) did not change the course of enteral nutrition management during drug treatment for patent ductus arteriosus, and 29 NICUs (48.3%) instated NPO for 1 or 2 feeds during blood transfusion. CONCLUSION: There were significant differences in human milk feeding and enteral feeding strategies between the NICUs in CHNN, but also similarities. The data obtained would be useful in the establishment of national enteral feeding guidelines for preterm infants and quality improvement of cooperation at the national level.

Novel cellular senescence-related risk model identified as the prognostic biomarkers for lung squamous cell carcinoma.

Background: Lung cancer is one of the top causes of cancer-related death worldwide. Cellular senescence is a characteristic of cell cycle arrest that plays a role in carcinogenesis and immune microenvironment modulation. Despite this, the clinical and immune cell infiltration features of senescence in lung squamous cell carcinoma (LUSC) are unknown. Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were used to get RNA-seq data and clinical information for LUSC. The least absolute shrinkage and selection operator (LASSO)-Cox regression, receiver operating characteristic (ROC), and Kaplan-Meier analysis were used to evaluate a risk model for predicting overall survival based on six differentially expressed genes. The tumor microenvironment (TME) and immunotherapy response were also studied. Results: To discriminate LUSC into high- and low-risk subgroups, a risk model comprised of six cellular senescence-related genes (CDKN1A, CEBPB, MDH1, SIX1, SNAI1, and SOX5) was developed. The model could stratify patients into high-risk and low-risk groups, according to ROC and Kaplan-Meier analysis. In the TCGA-LUSC and GSE73403 cohorts, the high-risk group had a worse prognosis (P<0.05), and was associated with immune cell inactivation and being insensitive to immunotherapy in IMvigor210. Conclusions: We discovered a new LUSC classification based on six cellular senescence-related genes, which will aid in identifying patients who will benefit from anti-PD-1 treatment. Targeting senescence-related genes appears to be another option for improving clinical therapy for LUSC.

Identification of necroptosis-related signature and tumor microenvironment infiltration characteristics in lung adenocarcinoma.

OBJECTIVES: Lung cancer remains the most common cancer and the leading cause of cancer deaths. However, the potential roles of necroptosis-related signature and tumor microenvironment (TME) in the lung adenocarcinoma (LUAD) still unknown. MATERIALS AND METHODS: Expression data and clinical information were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. In the TCGA dataset, necroptosis phenotype-related differentially expressed genes (DEGs) were identified. A necroticscore score was developed and validated by integrating GEO-meta datasets. The clinical value of the risk score was further evaluated using Kaplan-Meier and immunotherapeutic cohort (IMvigor210 cohort). RESULTS: Three necroptosis-related patterns and distinct necroptosis-related gene cluster were identified based on the abnormal expression of 14 necroptosis regulators. The necroptosis genomic phenotypes were obtained based on 117 necroptosis phenotype-related DEGs. A necroticscore were constructed to evaluate necroptosis pattern of each patient. Low necroticscore was linked with decreased immune check-point expression, enhanced immune check-point inhibitor response, and better clinical benefits. CONCLUSION: This study suggested that the crucial roles of necroptosis-related regulators in modeling the heterogeneity of TME characteristics. Thus, assessing necroptosis patterns provided us with a deeper understanding of TME and might guide the clinical immunotherapy treatment of lung cancer.

[Influence of the coronavirus disease 2019 pandemic on maternal breastfeeding for very low birth weight infants]. / æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žç–«æƒ å¯¹æžä½Žå‡ºç”Ÿä½“é‡å„¿äº²æ¯æ¯ä¹³å–‚å »çš„å½±å“.

OBJECTIVES: To investigate the changes in the rate and volume of mother's own milk (MOM) feeding for very low birth weight infants (VLBWIs) hospitalized during the prevention and control of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A retrospective analysis was performed on the medical data of the VLBWIs with a gestational age of <32 weeks who were born and admitted to the Neonatal Intensive Care Unit of Nanjing Maternal and Child Health Hospital from January 2019 to December 2020. The changes in the rate and volume of MOM feeding for VLBWIs during hospitalization were examined. RESULTS: A total of 301 VLBWIs were enrolled. According to the timing of COVID-19 outbreak, these infants were divided into a pre-CIVID-19 group with 205 VLBWIs and a post-COVID-19 group with 96 VLBWIs. Compared with the pre-CIVID-19 group, the post-COVID-19 group had a significantly lower rate of MOM feeding within 28 days after birth and during hospitalization (P<0.05), a significantly lower volume of MOM feeding within 0-7 days, 0-14 days, and 0-28 days after birth (P<0.05), and significantly higher incidence rates of moderate-to-severe bronchopulmonary dysplasia and feeding intolerance (P<0.05). CONCLUSIONS: The COVID-19 pandemic has a significant impact on MOM feeding for VLBWIs, and there are significant reductions in the rate and volume of MOM feeding for VLBWIs within 28 days after birth, as well as a significant reduction in the rate of MOM feeding during hospitalization.

5-methylcytosine RNA methylation regulators affect prognosis and tumor microenvironment in lung adenocarcinoma.

Background: Accumulating evidence has shown that 5-methylcytosinec (m5C) RNA methylation plays an essential role in tumorigenesis. However, the roles of m5C regulators in the prognosis, tumor microenvironment (TME), and immunotherapy responses of lung adenocarcinoma (LUAD) have not been fully analyzed. Methods: Based on 14 m5C RNA regulators, we evaluated the m5C RNA modification patterns in patients with LUAD (n=594) in The Cancer Genome Atlas (TCGA). Unsupervised clustering analysis was performed to confirm distinct m5C modification patterns. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate the biological functions of differentially expressed genes (DEGs) among different m5C RNA modification patterns. An m5C signature (m5Csig) was constructed using least absolute shrinkage and selection operator (LASSO) algorithms. The GSE72094 cohort (n=442) from the Gene Expression Omnibus (GEO) was used to validate m5Csig. A receiver operating characteristic (ROC) model was constructed to evaluate the sensitivity and specificity of m5Csig. Tumor-infiltrating immune cells (TIICs) between the high- and low-risk groups were estimated using the Cell Type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm. Results: We identified 3 m5C RNA modification clusters. Overall survival (OS) differed among the 3 clusters. The m5Csig, including TRDMT1, NSUN1, NSUN4, NSUN7, and ALYREF, was constructed to classify patients with LUAD into high- and low-risk groups. The high-risk group, with more immune cell infiltration, had a significantly poorer OS than that the low-risk group, which was associated with better response to immune checkpoint blockade therapy. Conclusions: The present study revealed that m5C RNA regulators play a significant role in TME regulation in LUAD. The m5Csig can predict the prognosis of patients with LUAD and might provide novel strategies for tumor immunotherapy.

Molecular Characterization of the Clinical and Tumor Immune Microenvironment Signature of 5-methylcytosine-Related Regulators in non-small Cell Lung Cancer.

Background: DNA methylation is an important epigenetic modification, among which 5-methylcytosine methylation (5mC) is generally associated with tumorigenesis. Nonetheless, the potential roles of 5mC regulators in the tumor microenvironment (TME) remain unclear. Methods: The 5mC modification patterns of 1,374 lung adenocarcinoma samples were analyzed systematically. The correlation between the 5mC modification and tumor microenvironment cell infiltration was further assessed. The 5mCscore was developed to evaluate tumor mutation burden, immune check-point inhibitor response, and the clinical prognosis of individual tumors. Results: Three 5mC modification patterns were established based on the clinical characteristics of 21 5mC regulators. According to the differential expression of 5mC regulators, three distinct 5mC gene cluster were also identified, which showed distinct TME immune cell infiltration patterns and clinical prognoses. The 5mCscore was constructed to evaluate the tumor mutation burden, immune check-point inhibitor response, and prognosis characteristics. We found that patients with a low 5mCscore had significant immune cell infiltration and increased clinical benefit. Conclusion: This study indicated that the 5mC modification is involved in regulating TME infiltration remodeling. Targeting 5mC modification regulators might be a novel strategy to treat lung cancer.

An appendiceal mucinous neoplasm should be considered in the differential diagnosis of giant abdominopelvic tumor.

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[A clinical analysis of sepsis in very low birth weight infants].

OBJECTIVE: To study the incidence and clinical features of sepsis in very low birth weight (VLBW) infants. METHODS: The clinical data were collected from VLBW infants, with a birth weight of < 1 500 g, who were admitted to the Department of Neonatology, Maternity Hospital Affiliated to Nanjing Medical University, from January 2019 to June 2020. The incidence of sepsis, distribution of pathogenic bacteria, and risk factors for sepsis were analyzed. RESULTS: A total of 369 infants were enrolled, and 138 infants had sepsis, among whom 84 had early-onset sepsis (EOS) and 54 had late-onset sepsis (LOS). Enterococcus faecalis (24%) and Streptococcus (21%) were the main pathogenic bacteria in infants with EOS, and Staphylococcus (41%) and Enterobacter (29%) were the main pathogenic bacteria in infants with LOS. The incidence of EOS and LOS decreased with the increase of gestational age and birth weight (P < 0.05). The multivariate logistic regression analysis showed that a high birth weight was a protective factor against EOS (OR=0.996, 95%CI:0.993-0.998, P < 0.05), while vaginal delivery (OR=2.781, 95%CI:1.190-6.500, P < 0.05) was a risk factor for EOS, and long duration of parenteral nutrition was a risk factor for LOS (OR=1.129, 95%CI:1.067-1.194, P < 0.05). CONCLUSIONS: Enterococcus faecalis is the most common pathogenic bacteria for EOS, and Staphylococcus is the most common pathogenic bacterium for LOS in VLBW infants. A high birth weight may reduce the risk of EOS in VLBW infants, while vaginal delivery may increase the risk of EOS. Prolonged parenteral nutrition may increase the risk of LOS.

Molecular identification of an immunity- and Ferroptosis-related gene signature in non-small cell lung Cancer.

BACKGROUND: Lung cancer is one of the dominant causes of cancer-related deaths worldwide. Ferroptosis, an iron-dependent form of programmed cell death, plays a key role in cancer immunotherapy. However, the role of immunity- and ferroptosis-related gene signatures in non-small cell lung cancer (NSCLC) remain unclear. METHODS: RNA-seq data and clinical information pertaining to NSCLC were collected from The Cancer Genome Atlas dataset. Univariate and multivariate Cox regression analyses were performed to identify ferroptosis-related genes. A receiver operating characteristic (ROC) model was established for sensitivity and specificity evaluation. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to explore the function roles of differentially expressed genes. RESULTS: A signature composed of five ferroptosis-related genes was established to stratify patients into high- and low-risk subgroups. In comparison with patients in the low-risk group, those in the high-risk one showed significantly poor overall survival in the training and validation cohorts (P < 0.05). Multivariate Cox regression analysis indicated risk score to be an independent predictor of overall survival (P < 0.01). Further, the 1-, 2-, and 3-year ROCs were 0.623 vs. 0.792 vs. 0.635, 0.644 vs. 0.792 vs. 0.634, and 0.631 vs. 0.641 vs. 0.666 in one training and two validation cohorts, respectively. Functional analysis revealed that immune-related pathways were enriched and associated with abnormal activation of immune cells. CONCLUSIONS: We identified five immunity- and ferroptosis-related genes that may be involved in NSCLC progression and prognosis. Targeting ferroptosis-related genes seems to be an alternative to clinical therapy for NSCLC.

Helicobacter pylori-induced protein tyrosine phosphatase receptor type C as a prognostic biomarker for gastric cancer.

BACKGROUND: Helicobacter pylori (H. pylori) infection is closely associated with the tumorigenesis of gastric cancer. The aim of the present study was to identify the key regulator in H. pylori-related gastric cancer and to study the expression level and clinical value of the indicated key regulator in gastric cancer. METHODS: The GSE6143 dataset was used to identify differentially expressed genes (DEGs) with limma R package, and enrichment analysis was done using the Metascape web-based portal. The protein-protein interaction analysis was done using Search Tool for the Retrieval of Interacting Genes/Proteins. Gastric adenocarcinoma AGS and BGC-823 cells were treated with H. pylori strain 26695 to construct the in vitro H. pylori infection model, and quantitative reverse transcription polymerase chain reaction was used to analyze the mRNA levels of indicated genes. The correlation analysis between two genes in gastric cancer was done by GEPIA. Furthermore, the PTPRC expression by pathological features analysis was conducted in UALCAN, an easy to use, interactive web-portal (http://ualcan.path.uab.edu). The survival analysis for gastric cancer, based on PTPRC expression levels, was done using the Kaplan-Meier plotter. RESULTS: DEGs in gastric mucosa with or without H. pylori infection were identified and enriched in immune-related pathways and cancer pathways. The protein-protein interaction analysis confirmed the enrichment analysis of gene ontology. H. pylori strain 26695 exposure also confirmed the alteration of gene expression levels in AGS and BGC-823 cells. PTPRC was co-expressed with CSF2RB and TNFRSF7, indicating a significant positive correlation in gastric cancer. PTPRC was overexpressed in gastric cancer, and the overexpression of PTPRC was positively correlated with the progression of gastric cancer. Furthermore, the high expression of PTPRC could act as a poor prognostic factor for gastric cancer patients, especially for those at advanced stage. CONCLUSIONS: H. pylori-induced PTPRC is overexpressed in gastric cancer, and the overexpression of PTPRC is positively associated with the development of gastric cancer. The high expression of PTPRC could serve as poor prognostic biomarker for gastric cancer patients, especially for those at advanced stage. H. pylori-induced PTPRC is a prognostic biomarker for gastric cancer.

Preoperative pectoralis muscle radiodensity as a risk factor for postoperative complications after thoracoscopic lobectomy for non-small cell lung cancer.

BACKGROUND: Skeletal muscle radiodensity is associated with postoperative complications in cancer. However, data on skeletal muscle radiodensity and postoperative complication risk in patients with non-small cell lung cancer (NSCLC) are scarce, and this study investigated the relationship between skeletal muscle radiodensity and postoperative complication risk in patients with NSCLC treated by thoracoscopic lobectomy. METHODS: Quantitative and qualitative measurements of the pectoralis muscle were performed on a single axial slice above the aortic arch in the precontrast computed tomography (CT) scan performed before surgery. Sex-specific cutoffs for the pectoralis muscle mass index (PMI) and pectoralis muscle radiodensity (PMD) were set at the lowest tertile. A Clavien-Dindo grade ≥ III within 30 days of the operation was considered as a major complication, and logistic regression analysis was performed to identify risk factors for postoperative complications. RESULTS: The records of 163 consecutive patients with NSCLC receiving first-line thoracoscopic lobectomy between March 2016 and October 2019 were retrospectively reviewed and the PMI was found to be positively correlated with PMD (P<0.001). The PMI and PMD were significantly higher in men than in women (both P<0.001), and 23 (14.1%) patients experienced major postoperative complications. The multivariate analysis showed that male sex (P=0.032), lower body mass index (BMI) (P=0.016), and low PMD (P=0.012) before surgery, but not low PMI, were independent risk factors for major postoperative complications. CONCLUSIONS: Skeletal muscle quality but not muscle mass predicts major complications after thoracoscopic lobectomy for NSCLC. Skeletal muscle measures from the preoperative CT scan may be used to stratify patients with NSCLC into risk categories that can guide clinical decision-making.

An interesting dynamic ultrasound finding of pharyngoesophageal diverticulum: technical advice.

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Comment to: Effectiveness of contrast-enhanced ultrasound for detecting the staging and grading of bladder cancer: a systematic review and meta-analysis.

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Transcriptomic analysis reveals the role of a peptide derived from CRYAB on the CoCl2-induced hypoxic HL-1 cardiomyocytes.

Acute myocardial infarction (AMI) is a life-threatening disease that often results in heart failure. CRYAB, a small heat shock protein, has been shown to have cardioprotective effects against oxidative stress-induced apoptosis in AMI. Previously, we purified a peptide derived from CRYAB (LEDQFFGEH), which we named PDFC. In this study, we determined the function of PDFC on HL-1 cardiomyocytes and explored the mechanism underlying its function. A hypoxic myocardiocyte cell line was generated by stimulation of HL-1 mouse cardiac muscle cells with different concentrations of CoCl2. Then, the hypoxic HL-1 cells were treated with the synthetic PDFC peptide, and cell proliferation, migration, and apoptosis were assessed to examine the effects of PDFC on HL-1 and hypoxic HL-1 cells. To examine the mechanism underlying the effects of PDFC on hypoxic cells, PDFC-treated hypoxic HL-1 cells were submitted for deep RNA sequencing. Finally, several differentially expressed genes in different pathways were selected for confirmation by RT-qPCR. Hypoxic myocardiocytes were generated by stimulating HL-1 cells with 800 µM CoCl2 for 24 h, which significantly upregulated HIF-1α. PDFC at 200 µg/ml showed the most positive effects on cell viability. Although hypoxic HL-1 cells and PDFC-treated hypoxic HL-1 cells both showed lower viability and migration and higher levels of apoptosis than untreated HL-1 cells, compared to hypoxic HL-1 cells, PDFC-treated hypoxic HL-1 cells showed higher viability and migration and lower apoptosis. The deep sequencing showed that 812 genes were upregulated and 1946 genes were downregulated. Among these differentially expressed genes, 699 of the upregulated genes and 1488 of the downregulated genes were protein-coding genes. Gene ontology and pathway enrichment analysis showed that the downregulated genes were dominant and that the PI3K-Akt pathway was located in the center of the network. A protein-protein interaction network was constructed, and 892 nodes were determined. In PDFC-treated hypoxic HL-1 cells, Fn1, Pik3r5, and Creb5 were downregulated, while Insr, Bcl2, Mapk14, and Pten were upregulated when compared to the levels in hypoxic HL-1 cells. In conclusion, this study reveals the significant bioactive effect of the CRYAB-derived peptide, PDFC on cardiomyocytes and the underlying mechanism.

MicroRNA-375 overexpression disrupts cardiac development of Zebrafish (Danio rerio) by targeting notch2.

MicroRNAs are small noncoding RNAs that are important for proper cardiac development. In our previous study of fetuses with ventricular septal defects, we discovered that microRNA-375 (miR-375) is obviously upregulated compared with that in healthy controls. Our study also confirmed that miR-375 is crucial for cardiomyocyte differentiation. This research mainly focused on the biological significance and mechanism of miR-375 using a zebrafish model. We injected zebrafish embryos with 1-2 nl of a miR-375 mimic at various concentrations (0/2/4/8 µM) or with negative control. The deformation and mortality rates were separately assessed. The different expression levels of miR-375 and related genes were examined by qRT-PCR, and luciferase assays and in situ hybridization were used to clarify the mechanism of miR-375 during embryonic development. Overexpression of miR-375 disrupted the cardiac development of zebrafish embryos. Disruption of miR-375 led to a decreased heart rate, pericardial edema, and abnormal cardiac looping. Various genes involved in cardiac development were downregulated due to the overexpression of miR-375. Moreover, the NOTCH signaling pathway was affected, and the luciferase reporter gene assays confirmed notch2, which was predicted by bioinformatics analysis, as the target gene of miR-375. Our findings demonstrated that the overexpression of miR-375 is detrimental to embryonic development, including cardiac development, and can partially simulate a multisystemic disorder. MiR-375 has an important role during cardiac morphogenesis of zebrafish embryos by targeting notch2, indicating its potential as a diagnostic marker.

Profiles analysis reveals circular RNAs involving zebrafish physiological development.

Recent studies have found that known functions of circular RNAs (circRNAs) include sequestration of microRNAs (miRNAs) or proteins, modulation of transcription and interference with splicing, and even translation to produce polypeptides. The zebrafish model is also demonstrably similar to humans in many studies. To explore the changes in circRNAs during embryonic development and to further research the mechanism of action of circRNAs in development-related diseases, Zebrafish embryos at the blastula period, gastrula period, segmentation period, throat stage, and incubation period were collected. Illumina deep-sequencing technology and CircRNA Identifier (CIRI) algorithm were used to detect circRNAs. In total, we identified 1,028 circRNAs (junction reads ≥5 and p < 0.05). Considering that the function of circRNAs is related to host genes, a bioinformatics analysis revealed these differentially expressed host genes are involved in NOTCH signaling pathways, cardiovascular system development, retinal ganglion cell axon guidance, and so on. Moreover, circRNAs can participate in biological regulation through the function of miRNA sponges. TargetScan and miRanda were used to predict 73 miRNAs binding to circRNAs such as miR-19b, miR-124, and so on. Some miRNAs play important roles in embryogenesis. The peak expression of circRNAs is distributed at different time points, suggesting that it may be involved in embryogenesis at different stages. Our study provides a foundation for understanding the dynamic regulation of circRNA transcriptomes during embryogenesis and identifies novel key circRNAs that might control embryonic development in a zebrafish model.