Association between late bedtime and obesity in children and adolescents: a meta-analysis.

Background: Short sleep duration has been related to obesity in children and adolescents. However, it remains unknown whether late bedtime is also associated with obesity and whether the association is independent of sleep duration. A meta-analysis was performed to address this issue. Methods: In order to accomplish the aim of the meta-analysis, a comprehensive search was conducted on databases including PubMed, Embase, and Web of Science to identify observational studies. The cutoff to determine late bedtime in children in this meta-analysis was consistent with the value used among the included original studies. As for obesity, it was typically defined as a body mass index (BMI) > 95th percentile of age and sex specified reference standards or the International Obesity Task Force defined age- and gender-specific cut-off of BMI. The Cochrane Q test was employed to evaluate heterogeneity among the included studies, while the I2 statistic was estimated. Random-effects models were utilized to merge the results, considering the potential impact of heterogeneity. Results: Tweleve observational studies with 57,728 participants were included. Among them, 6,815 (11.8%) were obese. Pooled results showed that late bedtime reported by the participants or their caregivers was associated with obesity (odds ratio [OR]: 1.27, 95% confidence interval [CI]: 1.16-1.39, p < 0.001; I2 = 0%). Subgroup analysis showed consistent results in studies with (OR: 1.33, 95% CI: 1.04-1.70, p = 0.02) and without adjustment of sleep duration (OR: 1.27, 95% CI: 1.14-1.41, p < 0.001). Further subgroup analysis also showed that the association was not significantly affected by study location, design, age of the participants, or diagnostic methods for obesity (p for subgroup difference all >0.05). Conclusion: Late bedtime is associated with obesity in children and adolescents, which may be independent of sleep duration.

Genome-wide analysis of RNA-binding protein co-expression with alternative splicing events in acute respiratory distress syndrome following hematopoietic stem cell transplantation.

Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are at an increased risk of developing severe acute respiratory distress syndrome (ARDS), which is characterized by peripheral bilateral patchy lung involvement. The regulatory network of RNA-binding protein (RBP)-alternative splicing (AS) in ARDS following HSCT has not been investigated. We hypothesize that RBP-AS plays a regulatory role during HSCT-ARDS. The published ARDS transcriptome data after HSCT (GSE84439) were downloaded, and the transcriptome data of 13 mRNAs were obtained by sequencing the peripheral blood of 5 HSCT-ARDS patients and 8 ARDS patients through high-throughput sequencing technology. Systematic analysis of downloaded data was performed to obtain differentially expressed RBPs, and the differentially alternative spliced pre-mRNAs in HSCT-ARDS and control groups were used to explore the global gene RBP-AS regulatory network. A total of 1769 differentially expressed genes and 4714 regulated alternative splicing events were identified in peripheral blood from HSCT-ARDS, of which 254 genes had both differential expression and differential AS. In addition, 128 RBPs were identified, of which HDGF, PCBP2, RIOK3, CISD2, and TRIM21, DDX58, MOV10 showed significantly increased or decreased expression in the HSCT-ARDS. RBPs with decreased expression had antiviral activity, while those with increased expression were involved in ROS, fibrosis, and negative viral resistance. The RBP-RASE-RASG regulatory network is constructed. It is related to the dysregulation of antiviral immunomodulation, imbalance in ROS homeostasis and pro-pulmonary fibrosis, which are involved in the development of HSCT-ARDS.

Loss of LEAP-2 alleviates obesity-induced myocardial injury by regulating macrophage polarization.

BACKGROUND: Obesity is a serious public health issue worldwide, which is a risk factor of cardiovascular disorders. Obesity has been shown to be associated with subclinical myocardial injury, increasing the risk of heart failure. Our study aims to explore novel mechanisms underlying obesity-induced myocardial injury. METHODS: Mice were fed a high-fat diet (HFD) to establish a mouse model of obesity, and serum levels of TG, TCH, LDL, CK-MB, LDH, cTnI and BNP were examined. Inflammatory response was evaluated by determining the expression and secretion of proinflammatory cytokines IL-1ß and TNF-α. Macrophage infiltration in the heart was examined by IHC staining, and H&E staining was applied to evaluate myocardial injury. Primary peritoneal macrophages were isolated from mice and treated with palmitic acid (PA). Macrophage polarization was evaluated by determine the expression of CCL2, iNOS, CD206 and arginase I via Western blot, RT-qPCR, and flow cytometry. Co-IP assays were performed to examine the interaction between LEAP-2, GHSR and ghrelin. RESULTS: Hyperlipidemia, increased proinflammatory cytokines and myocardial injury were observed in mice with obesity, and silencing of LEAP-2 ameliorated HFD-induced hyperlipidemia, inflammation, and myocardial injury. Moreover, HFD-induced macrophage infiltration and M1 polarization were reversed by LEAP-2 knockdown in mice. Furthermore, silencing of LEAP-2 suppressed PA-induced M1 polarization but enhanced M2 polarization in vitro. LEAP-2 interacted with GHSR in macrophages, and knockdown of LEAP-2 promoted the interaction of GHSR and ghrelin. Overexpression of ghrelin enhanced LEAP-1 silencing-mediated suppression of inflammatory response and upregulation of M2 polarization in PA-induced macrophages. CONCLUSION: Knockdown of LEAP-2 ameliorates obesity-induced myocardial injury via promoting M2 polarization.

Accurate and Rapid Diagnosis of Complex Mitral Valve Aneurysm with Neoplasm via Real-time 3D Transesophageal Echocardiography.

Mitral valve leaflet aneurysm (MVA) is a rare and potentially devastating complication of infective endocarditis. Here, we report the case of a 49-year-old man with mitral endocarditis who had an anterior MVA without aortic morphologic change and only mild regurgitation. By real-time 3D transesophageal echocardiography (TOE), we found two perforations and a hard mass in the aneurysm accompanied with severe regurgitation. The patient underwent valve replacement surgery combined with anti-infection treatment and was successfully discharged. In addition to the case report and literature review related to MVA, we also summarize the application value of RT-3D TOE in these cases.

Ghrelin Relieves Obesity-Induced Myocardial Injury by Regulating the Epigenetic Suppression of miR-196b Mediated by lncRNA HOTAIR.

INTRODUCTION: Obesity has been believed to be closely linked with many kinds of diseases including atherosclerosis, hypertension, cerebrovascular thrombosis, and diabetes. Ghrelin and Homeobox transcript antisense RNA (HOTAIR) were believed to be involved in the regulation of myocardial injury. METHODS: The obesity mice model was established through feeding mice (C57BL/6J, male, eight-week-old) with high-fat diet and palmitate (PA)-induced cardiomyocyte injury. RNA and protein levels were detected with Quantitative real-time PCR and Western blotting. The levels of TG, TCH, LDL, CK-MB, cTnl, and BNP in the serum or cell medium supernatant were measured using ELISA kits. The ROS level was detected with the DCFH-DA method. Binding sites between different targets were identified using detection of dual luciferase reporter assay. Cell apoptosis was analyzed by flow cytometry. RNA-binding protein immunoprecipitation and chromatin immunoprecipitation were used to detect the binding of DNMT3B with HOTAIR or miR-196b promoter. RESULTS: The expression of HOTAIR was downregulated, and miR-196b was upregulated in the obese myocardial injury. Ghrelin attenuated PA-induced cardiomyocyte injury by increasing HOTAIR. HOTAIR regulated the expression of miR-196b by recruiting DNMT3B to induce methylation of the miR-196b gene promoter. The binding site between miR-196b and IGF-1 was identified. DISCUSSION/CONCLUSION: We demonstrated that ghrelin attenuated PA-induced cardiomyocyte injury by regulating the HOTAIR/miR-196b/IGF-1 signaling pathway. Our findings might provide novel thought for the prevention and treatment of obesity-induced myocardial injury by targeting HOTAIR/miR-196b.

MicroRNAs target the Wnt/ß­catenin signaling pathway to regulate epithelial­mesenchymal transition in cancer (Review).

Epithelial­mesenchymal transition (EMT), during which cancer cells lose the epithelial phenotype and gain the mesenchymal phenotype, has been verified to result in tumor migration and invasion. Numerous studies have shown that dysregulation of the Wnt/ß­catenin signaling pathway gives rise to EMT, which is characterized by nuclear translocation of ß­catenin and E­cadherin suppression. Wnt/ß­catenin signaling was confirmed to be affected by microRNAs (miRNAs), several of which are down­ or upregulated in metastatic cancer cells, indicating their complex roles in Wnt/ß­catenin signaling. In this review, we demonstrated the targets of various miRNAs in altering Wnt/ß­catenin signaling to promote or inhibit EMT, which may elucidate the underlying mechanism of EMT regulation by miRNAs and provide evidence for potential therapeutic targets in the treatment of invasive tumors.

Ghrelin protects against obesity-induced myocardial injury by regulating the lncRNA H19/miR-29a/IGF-1 signalling axis.

BACKGROUND: Obesity is associated with the impairment of cardiac fitness and consequent ventricular dysfunction and heart failure. Ghrelin has been largely documented to be cardioprotective against ischaemia/reperfusion injury. However, the role of ghrelin in obesity-induced myocardial injury is largely unknown. This study sought to determine the cardiac effect of ghrelin against obesity-induced injury and the underlying mechanisms. METHODS: The effect of ghrelin was evaluated in a mouse model of obesity and a palmitic acid (PA)-treated cardiomyocyte cell line with or without ghrelin transfection. Gene and protein expression levels were determined by real-time PCR and western blot, respectively. Cell apoptosis was measured by flow cytometry analysis. RESULTS: In the present study, we found that both a high-fat diet (HFD) and PA treatment caused myocardial injury by increasing apoptosis and the expression of inflammatory cytokines. Overexpression of ghrelin reversed the effects induced by HFD or PA treatment. Knockdown of lncRNA H19 or overexpression of miR-29a abrogated the cardioprotective effects of ghrelin against apoptosis and inflammation. We also found that IGF-1 was a target gene of miR-29a and that H19 regulated IGF-1 expression via miR-29a. Overexpression of IGF-1 partially reversed the apoptosis and inflammation promoting effects of miR-29a. CONCLUSIONS: Our findings suggested that ghrelin protected against obesity-induced myocardial injury by regulating the H19/miR-29a/IGF-1 signalling axis, providing further evidence for the clinical application of ghrelin.

Potent influenza A virus entry inhibitors targeting a conserved region of hemagglutinin.

Influenza A viruses (IAVs) induce acute respiratory disease and cause significant morbidity and mortality throughout the world. With the emergence of drug-resistant viral strains, new and effective anti-IAV drugs with different modes of action are urgently needed. In this study, by conjugating cholesterol to the N-terminus of the short peptide KKWK, a lipopeptide named S-KKWK was created. The anti-IAV test indicated that S-KKWK and its derivatives displayed potent antiviral activities against a broad variety of influenza A viral strains including oseltamivir-resistant strains and clinically relevant isolates with IC50 values ranging from 0.7 to 3.0µM. An extensive mechanistic study showed that these peptides functioned as viral "entry blockers" by inhibiting the conformational rearrangements of HA2 subunit, thereby interrupting the fusion of virus-host cell membranes. Significantly, a computer-aided docking simulation and protein sequence alignment identified conserved residues in the stem region of HA2 as the possible binding site of S-KKWK, which may be employed as a potential drug target for designing anti-IAVs with a broad-spectrum of activity. By targeting this region, a potent anti-IAV agent was subsequently created. In addition, the anti-IAV activity of S-KKWK was assessed by experiments with influenza A virus-infected mice, in which S-KKWK reduced the mortality of infected animals and extended survival time significantly. Overall, in addition to providing a strategy for designing broad-spectrum anti-IAV agents, these results indicate that S-KKWK and its derivatives are prospective candidates for potent antivirals.

A field-programmable-gate-array based time digitizer for the time-of-flight mass spectrometry.

The time-of-flight (TOF) mass spectrometry is one of the most widely used techniques to get information about the composition and structure of compounds. The time digitizer, based on time-to-digital conversion, is one of the important parts in modern TOF mass spectrometry, which is often implemented with analog circuitry or application-specific-integrated-circuit (ASIC) devices. However, it is difficult to achieve a high density with the analog approach. Furthermore, ASIC requires a long design cycle and the function cannot be easily revised for different applications. In this work, we present a highly flexible, accurate, yet low-costing design of time digitizer which is based on a field-programmable-gate-array (FPGA) and time interpolation method. Test results indicate that the bin size of this time digitizer is 390 ps with an average standard deviation (about 150 ps). The differential nonlinearity is in the range of -0.10 to +0.05 LSB (least significant bit), and the measurement time range is larger than 107 s. Compared with other techniques, it reduces the system complexity while providing a good flexibility. In addition, this technique can also accommodate one or more STOP pulse measurements for each START pulse reference, enabling measurement of multiple times-of-flight with a common start trigger. Besides, a time stamp is recorded for each input pulse, rendering this time digitizer versatile in other applications. Moreover, because of the programmable characteristic of a FPGA, more functions can be integrated in the time digitizer, such as a trigger function, data transfer interface; the parameters such as the number of the channels. The measurement range can also be modified according to different requirements.

[Relationship between angiotensin converting enzyme gene polymorphism and essential hypertension in children].

OBJECTIVE: To study the relationship between insertion/deletion (I/D) polymorphism of 287 bp in the 16th intron of angiotensin converting enzyme (ACE) and essential hypertension in children. METHODS: I/D polymorphism of 287 bp in the 16th intron of ACE was detected using PCR in 105 children with essential hypertension and 105 normal children as control group. RESULTS: There was an I/D polymorphism in the 16th intron of ACE in the hypertension and the control groups: type II, type ID and type DD. The genotype frequencies of type DD, type ID and type II in the hypertension group were 30.5%, 47.6% and 21.9%, respectively. The genotype frequencies of type DD, type ID and type II in the control group were 14.3%, 46.7% and 39.1%, respectively. There were significant differences in the genotype frequencies of types DD and II between the two groups (P<0.01). The allele frequency of type D (54.3% vs 37.6%) was significantly higher in the hypertension group; in contrast, the allele frequency of type I (45.7% vs 62.4%) was significantly lower than in the control group (P<0.01). CONCLUSIONS: Polymorphism of type II, type ID and type DD exits in ACE. The deletion of 287 bp in the 16th intron of ACE might be associated with the occurrence of essential hypertension in children.