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In the past studies, it is shown that cardiac troponin I (cTnI, encoded by TNNI3), as a cytoplasmic protein, is an inhibitory subunit in troponin complex, and involves in cardiomyocyte diastolic regulation. Here, we assessed a novel role of cTnI as a nucleoprotein. Firstly, the nuclear translocation of cTnI was found in mouse, human fetuses and rat heart tissues. In addition, there were differences in percentage of intranuclear cTnI in different conditions. Based on weighted gene co-expression network analyses (WGCNA) and verification in cell experiments, a strong expression correlation was found between TNNI3 and Atp2a2, which encodes sarco-endoplasmic reticulum Ca2+ ATPase isoform 2a (SERCA2a), and involves in ATP hydrolysis and Ca 2+ transient. TNNI3 gain and loss caused Atpa2a2 increase/decrease in a dose-dependent manner both in mRNA and protein levels, in vivo and in vitro. By using ChIP-sequence we demonstrated specific binding DNA sequences of cTnI were enriched in ATP2a2 promoter −239∼-889 region and the specific binding sequence motif of cTnI was analyzed by software as "CCAT", which has been reported to be required for YY1 binding to the promoter region of YY1-related genes. Moreover, it was further verified that pcDNA3.1 (−)-TNNI3 could express cTnI proteins and increase the promoter activity of Atp2a2 through luciferase report assay. In the end, we evaluated beat frequencies, total ATP contents, Ca 2+ transients in TNNI3-siRNA myocardial cells. These findings indicated, for the first time, cTnI may regulate Atp2a2 in cardiomyocytes as a co-regulatory factor and participate in the regulation of intracellular Ca ions.

Due to the impact of the new crown pneumonia outbreak, offline teaching was conducted to varying degrees in schools and universities nationwide in spring 2020. After the epidemic was effectively controlled, students in various schools around the country returned to school one after another, and offline teaching was resumed. In order to deeply promote it, the School of Marxism of Guangdong Second Normal College developed and built an on-campus online open course on “Outline of Modern Chinese History” and carried out the reform and practice of a hybrid teaching on the basis of abandoning traditional teaching. The reform and practice of online teaching go hand in hand. Information technology is a high-tech product; hybrid teaching is a new thing; reform of Civics and Political Science class should be combined with the actual front-line teaching, for students’ ideas and cognitive characteristics of continuous improvement and student growth. Due to some shortcomings of the process of the current teaching mode of college teaching, such as large evaluation errors and long time, the paper proposed the evaluation method of college teaching mode with the goal of improving the accuracy of college teaching mode evaluation. Firstly, we analyze the current research status of college teaching mode evaluation and find the reasons for the poor results of current college teaching mode evaluation; then, we collect the college teaching mode evaluation data, adopt deep learning algorithm to learn the college teaching mode evaluation data, and establish the college teaching mode evaluation model; finally, we conduct the application example test of college teaching mode evaluation.

The purpose of this study was to explore a new algorithm model capable of leverage deep learning to screen and diagnose specific types of left-to-right shunt congenital heart disease (CHD) in children.Using deep learning, screening models were constructed to identify 884 heart sound recordings from children with left-to-right shunt CHD. The most suitable model for each type was summarized and compared with expert auscultation. An exploratory analysis was conducted to assess whether there were correlations between heart sounds and left ventricular ejection fraction (LVEF), pulmonary artery pressure, and malformation size.The residual convolution recurrent neural network (RCRnet) classification model had higher accuracy than other models with respect to atrial septal defect (ASD), ventricular septum defect (VSD), patent ductus arteriosus (PDA) and combined CHD, and the best auscultation sites were determined to be the 4th, 5th, 2nd and 3rd auscultation areas, respectively. The diagnostic results of this model were better than those derived from expert auscultation, with sensitivity values of 0.932-1.000, specificity values of 0.944-0.997, precision values of 0.888-0.997 and accuracy values of 0.940-0.994. Absolute Pearson correlation coefficient values between heart sounds of the four types of CHD and LVEF, right ventricular systolic pressure (RVSP) and malformation size were all less than 0.3.The RCRnet model can preliminarily determine types of left-to-right shunt CHD and improve diagnostic efficiency, which may provide a new choice algorithmic CHD screening in children.

Purpose To compare the use of single‑pass four‑throw (SFT) and traditional double-pass two-throw knotting (DTT) techniques in pupilloplasty for traumatic mydriasis combined with lens dislocation, and to evaluate the learning curve between the two knotting techniques by wet lab. Method The eyes of 45 patients (45 eyes) were divided into two groups according to the knotting technique used: single‑pass four‑throw (22 eyes) or traditional double-pass-two-throw knotting (23 eyes). Combined phacoemulsification and pupilloplasty with pars plana vitrectomy were performed in traumatic mydriasis patients with lens dislocation. Preoperative and postoperative corrected distance visual acuity (CDVA), pupil diameter, intraocular pressure (IOP), pupilloplasty time, and complications were compared. Twenty ophthalmology residents were randomized to perform a pupilloplasty suturing exam with or without SFT knotting techniques in porcine eyes. Result All cases had a minimum follow‑up period of 6 months (range 6–12 months). There was no significant difference in the CDVA (P = 0.55), postoperative pupil diameter (P = 0.79), IOP (P > 0.05), anterior chamber exudate degree, and loosening or shedding of the line knot between the two groups. The duration of the pupilloplasty was 22.32 ± 4.58 min in the SFT group and 30.35 ± 5.55 min in the traditional group, which was a significant difference (P P Conclusion The SFT knotting technique has a similar treatment effect and safety as the traditional technique but requires a shorter time and is easier to perform in pupilloplasty surgery.

By simulating the dependence of laser directionality and the possibility of multimode lasing on the sidewall angle of Aquarius-shaped cavity, we achieved the optimized parameters for low-coherence and high-directivity laser output. The measured divergence angle, the speckle contrast, and the output power are 7.2°, 4.53 %, 700 mW@4 A, respectively, in the experiment. Then we introduced patterned electrode on the P-side of the laser, and obtained adjustable coherence with the switched speckle contrast between 4.8 % and 27.8 %. This highly directional and adjustable coherence on-chip complex cavity laser prospectively offers a new choice for biological imaging.

AimsEpilepsy is a neurological disease occurring worldwide. Alterations in the gut microbial composition may be involved in the development of Epilepsy. The study aimed to investigate the effects of cannabidiol (CBD) on gut microbiota and the metabolic profile of epileptic rats.Materials and methods and resultsA temporal lobe epilepsy rat model was established using Li-pilocarpine. CBD increased the incubation period and reduced the epileptic state in rats. Compared to epileptic rats, the M1/M2 ratio of microglia in the CBD group was significantly decreased. The expression of IL-1β, IL-6, and TNF-α in the CBD group decreased, while IL-10, IL-4, and TGF-β1 increased. 16S rDNA sequencing revealed that the ANOSIM index differed significantly between the groups. At the genus level, Helicobacter, Prevotellaceae_UCG-001, and Ruminococcaceae_UCG-005 were significantly reduced in the model group. CBD intervention attenuated the intervention effects of Li-pilocarpine. Roseburia, Eubacterium_xylanophilum_group, and Ruminococcus_2 were strongly positively correlated with proinflammatory cytokine levels. CBD reversed dysregulated metabolites, including glycerophosphocholine and 4-ethylbenzoic acid.ConclusionCBD could alleviate the dysbiosis of gut microbiota and metabolic disorders of epileptic rats. CBD attenuated Epilepsy in rats might be related to gut microbial abundance and metabolite levels.Significance and impact of studyThe study may provide a reliable scientific clue to explore the regulatory pathway of CBD in alleviating Epilepsy.

BackgroundDermatomyositis is an autoimmune disease characterized by damage to the skin and muscles. CD4+ T cells are of crucial importance in the occurrence and development of dermatomyositis (DM). However, there are few bioinformatics studies on potential pathogenic genes and immune cell infiltration of DM. Therefore, this study intended to explore CD4+ T-cell infiltration–associated key genes in DM and construct a new model to predict the level of CD4+ T-cell infiltration in DM.MethodsGSE46239, GSE142807, GSE1551, and GSE193276 datasets were downloaded. The WGCNA and CIBERSORT algorithms were performed to identify the most correlated gene module with CD4+ T cells. Matascape was used for GO enrichment and KEGG pathway analysis of the key gene module. LASSO regression analysis was used to identify the key genes and construct the prediction model. The correlation between the key genes and CD4+ T-cell infiltration was investigated. GSEA was performed to research the underlying signaling pathways of the key genes. The key gene-correlated transcription factors were identified through the RcisTarget and Gene-motif rankings databases. The miRcode and DIANA-LncBase databases were used to build the lncRNA-miRNA-mRNA network.ResultsIn the brown module, 5 key genes (chromosome 1 open reading frame 106 (C1orf106), component of oligomeric Golgi complex 8 (COG8), envoplakin (EVPL), GTPases of immunity-associated protein family member 6 (GIMAP6), and interferon-alpha inducible protein 6 (IFI6)) highly associated with CD4+ T-cell infiltration were identified. The prediction model was constructed and showed better predictive performance in the training set, and this satisfactory model performance was validated in another skin biopsy dataset and a muscle biopsy dataset. The expression levels of the key genes promoted the CD4+ T-cell infiltration. GSEA results revealed that the key genes were remarkably enriched in many immunity-associated pathways, such as JAK/STAT signaling pathway. The cisbp_M2205, transcription factor-binding site, was enriched in C1orf106, EVPL, and IF16. Finally, 3,835 lncRNAs and 52 miRNAs significantly correlated with key genes were used to build a ceRNA network.ConclusionThe C1orf106, COG8, EVPL, GIMAP6, and IFI6 genes are associated with CD4+ T-cell infiltration. The prediction model constructed based on the 5 key genes may better predict the level of CD4+ T-cell infiltration in damaged muscle and lesional skin of DM. These key genes could be recognized as potential biomarkers and immunotherapeutic targets of DM.

ObjectiveThe clinical manifestations of ataxia–telangiectasia (AT) are very complex and are easily misdiagnosed and missed. The purpose of this study was to explore the clinical characteristics and genetic features of five pediatric patients with AT from three pedigrees in china.MethodsRetrospectively collected and analyzed the clinical data and genetic testing results of five AT patients diagnosed by the Whole-exome sequencing followed by Sanger sequencing. The five patients with AT were from three pedigrees, including two female patients (case 1 and case 2) in pedigree I, one male patient (case 3) in pedigree II, and two male patients (case 4 and case 5) in pedigree III. According to the United Kingdom Association for Clinical Genomic Science Best Practice Guidelines for Variants Classification in Rare Disease 2020 to grade the genetic variants.ResultsFive patients had mainly clinical presentations including unsteady gait, dysarthria, bulbar conjunctive telangiectasia, cerebellar atrophy, intellectual disability, stunted growth, increase of alpha-fetoprotein in serum, lymphopenia. Notably, one patient with classical AT presented dystonia as the first symptom. One patient had recurrent infections, five patients had serum Immunoglobulin (Ig) A deficiency, and two patients had IgG deficiency. In three pedigrees, we observed five pathogenic variants of the ATM gene, which were c.1339C>T (p.Arg447Ter), c.7141_7151delAATGGAAAAAT (p.Asn2381GlufsTer18), c.437_440delTCAA (p.Leu146GlnfsTer6), c.2482A>T (p.Lys828Ter), and c.5495_5496+2delAAGT (p.Glu1832GlyfsTer4). Moreover, the c.437_440delTCAA, c.2482A>T, and c.5495_5496+2delAAGT were previously unreported variants.ConclusionsPediatric patients with classical AT may present dystonia as the main manifestation, or even a first symptom, besides typical cerebellar ataxia, bulbar conjunctive telangiectasia, etc. Crucially, we also found three novel pathogenic ATM gene variants (c.437_440delTCAA, c.2482A>T, and c.5495_5496+2delAAGT), expanding the ATM pathogenic gene mutation spectrum.

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease (CTD), the main features of which are multiple serum autoantibodies and extensive involvement of multiple systems. The onset age of patients varies from childhood to middle age, with nearly 1/5 in childhood. Sjogren’s syndrome (SS) is also an autoimmune disease characterized by high-degree lymphocytic infiltration of exocrine glands, usually occurring in middle-aged and older women, and rarely in childhood. Neuromyelitis optica spectrum disorder (NMOSD) is an immune-mediated inflammatory demyelinating disease of the central nervous system (CNS) mainly involving the optic nerve and spinal cord. The coexistence of NMOSD and SLE and/or SS is well recognized by both neurologists and rheumatologists, but cases in children have been rarely reported. In this paper, we reported a case of a girl with onset at age 5 clinically featured by recurrent parotid gland enlargement, pancytopenia, hypocomplementemia, multiple positive serum antibodies, and cirrhosis. She was initially diagnosed with SS/SLE overlap syndrome at age 5. Four years later, the patient suffered a sudden vision loss and was examined to have positive AQP4 antibodies in serum and cerebrospinal fluid (CSF), and long segmental spinal swelling, in line with the diagnostic criteria for NMOSD. Up to now, the current patient is of the youngest onset age to develop SS/SLE coexisting with NMOSD, also with cirrhosis. It is important for clinicians to be aware of the possibility of CTDs coexisting with NMOSD in children, especially in those with positive anti-multiple autoantibodies, and to decrease the rate of missed diagnosis.

The clinical manifestations of ataxia-telangiectasia (AT) are very complex and are easily misdiagnosed and missed. The purpose of this study was to explore the clinical characteristics and genetic features of five pediatric patients with AT from three pedigrees in china.Retrospectively collected and analyzed the clinical data and genetic testing results of five AT patients diagnosed by the Whole-exome sequencing followed by Sanger sequencing. The five patients with AT were from three pedigrees, including two female patients (case 1 and case 2) in pedigree I, one male patient (case 3) in pedigree II, and two male patients (case 4 and case 5) in pedigree III. According to the United Kingdom Association for Clinical Genomic Science Best Practice Guidelines for Variants Classification in Rare Disease 2020 to grade the genetic variants.Five patients had mainly clinical presentations including unsteady gait, dysarthria, bulbar conjunctive telangiectasia, cerebellar atrophy, intellectual disability, stunted growth, increase of alpha-fetoprotein in serum, lymphopenia. Notably, one patient with classical AT presented dystonia as the first symptom. One patient had recurrent infections, five patients had serum Immunoglobulin (Ig) A deficiency, and two patients had IgG deficiency. In three pedigrees, we observed five pathogenic variants of thePediatric patients with classical AT may present dystonia as the main manifestation, or even a first symptom, besides typical cerebellar ataxia, bulbar conjunctive telangiectasia, etc. Crucially, we also found three novel pathogenic

Dermatomyositis is an autoimmune disease characterized by damage to the skin and muscles. CD4GSE46239, GSE142807, GSE1551, and GSE193276 datasets were downloaded. The WGCNA and CIBERSORT algorithms were performed to identify the most correlated gene module with CD4In the brown module, 5 key genes (chromosome 1 open reading frame 106 (The

MG53 is an important membrane repair protein and partially protects bone marrow multipotent adult progenitor cells (MAPCs) against oxidized low-density lipoprotein (ox-LDL). The present study was to test the hypothesis that the limited protective effect of MG53 on MAPCs was due to ox-LDL-induced reduction of MG53. MAPCs were cultured with and without ox-LDL (0-20 μg/mL) for up to 48 hours with or without MG53 and antioxidant N-acetylcysteine (NAC). Serum MG53 level was measured in ox-LDL-treated mice with or without NAC treatment. Ox-LDL induced significant membrane damage and substantially impaired MAPC survival with selective inhibition of Akt phosphorylation. NAC treatment effectively prevented ox-LDL-induced reduction of Akt phosphorylation without protecting MAPCs against ox-LDL. While having no effect on Akt phosphorylation, MG53 significantly decreased ox-LDL-induced membrane damage and partially improved the survival, proliferation and apoptosis of MAPCs in vitro. Ox-LDL significantly decreased MG53 level in vitro and serum MG53 level in vivo without changing MG53 clearance. NAC treatment prevented ox-LDL-induced MG53 reduction both in vitro and in vivo. Combined NAC and MG53 treatment significantly improved MAPC survival against ox-LDL. These data suggested that NAC enhanced the protective effect of MG53 on MAPCs against ox-LDL through preventing ox-LDL-induced reduction of MG53. ispartof: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE vol:24 issue:1 pages:886-898 ispartof: location:England status: published

BackgroundContinuous increasing nitrogen (N) deposition interferes with soil nitrogen cycle of forests, which highly impacts soil N2O emissions and accelerates global warming. Chinese fir (Cunninghamia lanceolata (Lamb.) Hook) is one of the most widely planted species in southern China which locates in the high N deposition area. However, the impact of N deposition on soil N2O emissions in subtropical Chinese fir plantations and the potential risk of increasing N deposition still remain elusive. Here, we conducted an in situ study in a subtropical Chinese fir plantation at Fengyang Mountain Nature Reserve, China, from 2019-2020 with four different levels of N enrichment: control (CK: ambient N deposition), low-N (LN: 50 kg N ha−1 yr−1), medium-N (MN: 100 kg N ha−1 yr−1), and high-N (HN: 200 kg N ha−1 yr−1). ResultsWe found that soil N2O emission rates increased with N enrichment from an average of 5.89 ± 3.66 to 20.11 ± 3.44 μg N m−2 h−1. The N enrichment in general showed no significant effect on the abundance of nitrate-reducing bacteria, but it tended to raise the abundance of ammonia oxidizing archaea and bacteria, and to decrease the abundance of N2O-reducing bacteria, which likely provided the microbial basis for accelerating soil N2O emissions along with increasing N deposition. However, the relationship of soil N2O emissions with N input did not match an exponential increase, but it matched a logarithmic increase, illustrating that the risk of increasing N deposition on soil N2O emissions was attenuated. It is found that N enrichment significantly decreased soil moisture and tended to increase the fir leaf N concentrations and soil CO2 emission rates. Besides, soil microbial biomass was significantly suppressed by N enrichment during the mid-growing season, while not in end of growing season. These may suggest that N enrichment stimulated plant growth with more N and water uptake, which competed with microorganisms for N and therefore alleviated further increasing N2O emissions under N enrichment. ConclusionThis study deepen our understanding of the impacts of increased N deposition on the greenhouse gas (GHG) balance in the Chinese fir plantations, and highlight that plants need to be incorporated as an important explanatory variable when predicting GHG fluxes in the background of global increasing N deposition.

The aim of this study was to investigate whether Treg/Th17 ratio regulation plays an important role in epigallocatechin-3-gallate (EGCG) in attenuating increased afterload-induced cardiac hypertrophy. Three-month-old male C57BL/6 mice were divided into sham + vehicle, abdominal aortic constriction (AAC) + vehicle, and AAC + EGCG groups. Intraperitoneal EGCG (50 mg/kg/d) administration was conducted. Cardiac structure and function were examined by ultrasonography. Pathology was examined by hematoxylin and eosin staining, wheat germ agglutinin staining, and Masson's trichome staining. T-lymphocyte subtypes were analyzed using immunofluorescence and flow cytometry assays. Ultrasonography showed that the ventricular wall in the AAC + vehicle group was thicker than that in the sham + vehicle group (P0.05). Hematoxylin and eosin staining revealed cardiomyocyte hypertrophy accompanied by a small amount of inflammatory cell infiltration in the AAC + vehicle group. The results of wheat germ agglutinin staining demonstrated the presence of hypertrophic cardiomyocytes in the AAC + vehicle group (P0.01). Masson's trichome staining showed cardiac fibrosis in the AAC + vehicle group, and the immunofluorescence assay revealed infiltration of CD4+ cells in both AAC + vehicle and AAC + EGCG groups. Splenic flow cytometry showed a significant increase in the proportion of Treg cells in the AAC + EGCG group (P0.05). The proportion of Th17 cells in the AAC + vehicle group was significantly higher than that in the sham + vehicle group (P0.05). In conclusion, changes in the Treg/Th17 ratio are associated with the occurrence of myocardial hypertrophy caused by increased afterload. Moreover, regulation of the Treg/Th17 ratio by EGCG may play an important role in the attenuation of myocardial hypertrophy.

GATA4 is a particularly important cardiogenic transcription factor and serves as a potent driver of cardiogenesis. Recent progress in the field has made it clear that histone acetylation can influence gene expression through changing the structure of chromatin. Our previous research had revealed that hypo-acetylation could repress gata4 expression in cardiocytes, however the underlying mechanism by which this occurred was still unclear. To reveal the mechanism of histone acetylation involved in the regulation of gata4 transcription, we concentrated on P300, one of the important histone acetyltransferase associated with cardiogenesis. We found that P300 participated in gata4 expression through regulating histone acetylation in embryonic mouse hearts. RNAi-mediated downregulation of P300 modulated the global acetylation of H3 and the acetylation of H3K4, H3K9, and H3K27 in gata4 and Tbx5 promoters. Interestingly, there was an obvious inhibition of gata4 transcription, whereas Tbx5 was not influenced. Furthermore, SGC-CBP30, the selective inhibitor of the bromodomain in CBP/P300, downregulated gata4 transcription by repressing the acetylation of H3K4, H3K9, and H3K27 in the gata4 promoters. Taken together, our results identified that acetylation of H3K4, H3K9, and H3K27 mediated by P300 plays an important role in regulation of gata4 expression in cardiogenesis.

Endothelial progenitor cells (EPCs) are a group of heterogeneous cells in bone marrow (BM) and blood. Ischaemia increases reactive oxygen species (ROS) production that regulates EPC number and function. The present study was conducted to determine if ischaemia‐induced ROS differentially regulated individual EPC subpopulations using a mouse model concomitantly overexpressing superoxide dismutase (SOD)1, SOD3 and glutathione peroxidase. Limb ischaemia was induced by femoral artery ligation in male transgenic mice with their wild‐type littermate as control. BM and blood cells were collected for EPCs analysis and mononuclear cell intracellular ROS production, apoptosis and proliferation at baseline, day 3 and day 21 after ischaemia. Cells positive for c‐Kit+/CD31+ or Sca‐1+/Flk‐1+ or CD34+/CD133+ or CD34+/Flk‐1+ were identified as EPCs. ischaemia significantly increased ROS production and cell apoptosis and decreased proliferation of circulating and BM mononuclear cells and increased BM and circulating EPCs levels. Overexpression of triple antioxidant enzymes effectively prevented ischaemia‐induced ROS production with significantly decreased cell apoptosis and preserved proliferation and significantly increased circulating EPCs level without significant changes in BM EPC populations, associated with enhanced recovery of blood flow and function of the ischemic limb. These data suggested that ischaemia‐induced ROS was differentially involved in the regulation of circulating EPC population.

Epigenetic regulations play an important role in disease development. In this study, we have investigated epigenetic regulations in restrictive cardiomyopathy mice with cTnI 193His mutation. Our results demonstrated that phosphodiesterase (PDEs) 4d was down-regulated in the heart of these mice. Further studies showed that the epigenetic modifications were associated with enhanced acetylation of histone 3 lysine 4 and lysines 9, whereas tri-methylation of histone 3 lysine 4, were decreased in histones near the PDE4d gene promoter regions. The binding levels of histone transmethylase SMYD1 and histone deacetylase HDAC1 were increased in the gene promoter regions in cTnI193His transgenic hearts. Using immune-fluorescent labeling we found an evidence of cTnI existence in the nucleus of cardiomyocytes and Western blotting further confirmed that both wild type and mutated cTnI could be detected in the cell nucleus of the hearts. Furthermore, an interaction between cTnI and SMYD1, or cTnI and HDAC1 was observed. Overexpression of the mutated cTnI in cultured cardiomyocytes reduced the expression of PDE4d. Our data suggest that the decrease of PDE4d expression in RCM mice caused by cTnI mutations may be related to epigenetic regulation, i.e., histone acetylation and methylation, and cTnI might be involved in this procedure via an interaction with HDAC1 and SMAD1 in the hearts.

Bladder cancer remains a very challenging disease to treat with the high rates of recurrence and progression associated with current therapies. Although the association between bladder cancer pathology and circRNAs remains undetermined, circRNAs signatures may be useful as prognostic and predictive factors and clinical tools for assessing disease state and outcome. This study investigates if these circRNAs can be used as biomarkers for bladder cancer diagnosis. Using bioinformatics method to analysis GEO databases (GSE37815, GSE39093, GSE97239, and GSE92675) for differentially expressed RNAs in bladder cancer and normal bladder tissues were screened from. The related volcanic maps and the interaction network maps of differentially expressed RNAs were drawn, and the mRNA-miRNA and miRNA-circRNA interaction were predicted to establish mRNA-miRNA-circRNA competitive endogenous RNA (ceRNA) network. The differential circRNAs related to prognosis of bladder cancer patients were screened based on the influence of miRNA interacting with the circRNA above on survival rate. The expression of miRNA (hsa-mir-214), circRNA (hsa_circ_0076704, hsa_circ_0081963, hsa_circ_0001361) in bladder cancer tissues, adjacent tissues, bladder cancer cells and normal bladder epithelial cells were validated by qRT-PCR. Kaplan Meier curve analysis confirmed the relationship between circRNA (hsa_circ_0076704) and overall survival and prognosis of bladder cancer patients. Through database screening and analysis, we found 19231 differentially expressed genes, 847 differentially expressed miRNAs, 7282 differentially expressed circRNAs. The establishment of ceRNA network consisted of 28 DERNAs (differentially- expressed RNAs), 12 Demi-RNAs and 12 DEcircRNAs. Further prognostic analysis showed that circRNA interacted miRNA hsa-miR-106b, hsa-miR-145 and hsa-miR-214 were associated with overall survival in patients with bladder cancer (P < 0.05). Among them, hsa_circ_0076704, hsa_circ_0081963 and hsa_circ_0001361 are potential circRNA related to OS in bladder cancer and expressed in bladder cancer. The expression of hsa-mir-214 was contrary. Further Kaplan Meier survival analysis showed that hsa_circ_0076704 had significant prognostic value (P < 0.05). In conclusion, hsa_circ_0076704 is independent prognostic factor for bladder cancer.

To investigate the mechanisms of potential cardioprotective effects of epigallocatechin-3-gallate (EGCG) in pressure overload-induced cardiac dysfunction.A chronic heart failure model was established using abdominal aortic constriction (AAC) surgery, rats were divided into sham, AAC, and AAC + EGCG groups. Echocardiography and tissue section staining were performed to evaluate cardiac function and pathology, respectively. Gene expression level were detected with quantitative real-time polymerase chain reactions. Label-free quantitative proteomics was used to investigate the whole proteomes of heart, and the differentially expressed proteins were analyzed using bioinformatics methods. Western blot was performed to validate the levels and the reliability of the differential proteins.Compared with the AAC group, systolic dysfunction was improved in AAC + EGCG group after EGCG treatment. EGCG inhibited myocardial fibrosis and cardiac hypertrophy after AAC, along with reducing atrial natriuretic protein, B-type natriuretic peptide, collagen types 1 and 3 alpha 1, and transforming growth factor β-1. Quantitative proteomics identified a total of 162 differentially expressed proteins, among them, 18 were closely related to cardiovascular disorders. Bioinformatics analyses showed that EGCG played a therapeutic role mainly by changing energy metabolism processes, such as oxidative phosphorylation and lipid metabolism. Furthermore, NADH: ubiquinone oxidoreductase subunit S4, an important component of the mitochondrial respiratory chain, was increased after AAC and then reversed by EGCG, which was consistent with the proteomics results.EGCG may correct cardiac systolic dysfunction and prevent cardiac remodeling after heart failure via enhancing the energy metabolism, which provides us with new insights into cardioprotective effects of EGCG related to the energy metabolisms in pressure overload-induced cardiac dysfunction.

Background and aims: E-selectin is a cell adhesion molecule of the vascular endothelium that mediates leukocyte rolling in the early inflammatory responses in many diseases including Kawasaki disease (KD). Previous studies have demonstrated that the expression levels of E-selectin was significantly increased in the sera of KD patients and in endothelial cells of KD patient's autopsy. In this study, we aimed to examine E-selectin levels in endothelial cells treated with sera from KD patients and explore the underlying mechanisms.Methods: Human coronary artery endothelial cells (HCAECs) were randomly incubated with sera from either healthy children [healthy control (HC group)] or pediatric KD patients [assigned as KD with coronary artery lesion (KD-CAL+ group) and KD without coronary artery lesion (KD-CAL– group)]. E-selectin levels were determined by RT-qPCR, Western blotting, and immunofluorescence. Cell adhesion assay was performed to quantify the role of E-selectin in intercellular adhesion. High-throughput cell RNA sequencing followed by functional validation was performed to explore the underlying mechanism.Results: E-selectin levels were significantly increased in KD-CAL+ group vs. HC group and KD-CAL– group. Compared with the KD-CAL– group, endothelia–monocyte adhesion was increased in the KD-CAL+ group, while E-selectin-specific siRNA could significantly rescue it. High-throughput cell RNA sequencing analysis also found a significant difference in oxidative phosphorylation (OXPHOS) levels between KD-CAL+ group and KD-CAL– group. Functional validation results further confirmed that the OXPHOS was upregulated in the KD-CAL+ group and KD-CAL– group compared to that in the HC group, while the KD-CAL+ group exhibited a higher OXPHOS than the KD-CAL– group. We also found that the E-selectin levels and endothelia–monocyte adhesion were significantly decreased by OXPHOS inhibitor oligomycin in the KD-CAL+ group and KD-CAL– group, respectively.Conclusion: Sera from KD patients stimulate OXPHOS levels and enhance E-selectin expression in HCAECs, which may contribute to the development of CAL in KD patients.

Malfunction of myocardial mitochondria plays a crucial role in the development of cardiovascular disorders, especially hypertrophic and dilated cardiomyopathies. Cardiac troponin I (cTnI) is an important structural protein and essential to contraction and relaxation of cardiomyocytes. Recent studies suggest that mutated cTnIR193H could function as a regulatory molecule for other cell functions. This study was to determine whether mutated cTnI could contribute to mitochondrial dysfunction of cardiomyocytes. Primary cardiomyocytes were transfected with cTnIR193H adenovirus with empty vector as control. Mitochondrial structure and function were evaluated in the cells 72 h after transfection. Transmission electron microscopy examination showed mitochondria in the cardiomyocytes with R193H mutation displayed broken cristae, vacuolation, and mitophagy. Mitochondrial function studies revealed a significant decrease in complex I activity, ATP and reactive oxygen species levels, and oxygen consumption rate compared with controls. Western blot analysis demonstrated that expressions of mitochondria-related genes, including ND5 (ubiquinone oxidoreductase chain 5), LRPPRC (a leucine-rich protein of pentatricopeptide repeat family), and PGC-1α (PPARG co-activator 1 alpha), were significantly downregulated in R193H mutation cardiomyocytes compared with the control. Swelling and broken cristae were observed in the mitochondria of cardiomyocytes from cTnIR193H mutation transgenic mice with decreased mitochondrial function, not from the littermate control mice. The data from the present study demonstrated that mitochondrial structure and function were significantly impaired in cardiomyocytes with cTnIR193H mutation, suggesting that cTnI might be critically involved in maintaining the structural and functional integrity of myocardial mitochondria.

Additional file 1: Figure S1. The size changes of IMTP-Fe3O4-PFH NPs for different days. Figure S2. The iron standard curves by atomic absorption spectroscopy. Figure S3. The routine blood indexes in the control group and the experimental groups. Figure S4. Morphology of normal H9C2 cells and cells treated with hypoxia for 24 h and 5 µmol/l of H2O2. Figure S5. Cell viability of H9C2 cells after treated with hypoxia for different duration and co-incubation with different concentrations of H2O2. Figure S6. Intra-operation and post-operation verification of ischemic myocardial model in rats. Figure S7. ADV and US imaging of IMTP-Fe3O4 NPs at different intensities of LIFU irritation and different time in vitro. Figure S8. The PA signal changes of IMTP-Fe3O4-PFH NPs irradiated by a laser at full spectrum ranging from 680 to 950 nm.

In the past studies, it is shown that cardiac troponin I (cTnI, encoded by

Yanan Zhang,1,2 Xiajing Chen,1,2 Lingjuan Liu,1,2 Jie Tian,1,2 Lan Hao,3 Hai-tao Ran3 1Department of Cardiology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China; 2Chongqing Key Laboratory of Pediatrics, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China; 3Chongqing Key Laboratory of Ultrasound Molecular Imaging & Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of ChinaCorrespondence: Jie TianDepartment of Cardiology, Children’s Hospital of Chongqing Medical University, 136 Zhongshan Er Road, Yu Zhong District, Chongqing, 400014, People’s Republic of ChinaTel +86 23 68486767Fax +86 23 68485111Email jietian@cqmu.edu.cnBackground and Purpose: Myocardial infarction (MI) is a serious threat to public health. The early identification of MI is important to promote appropriate treatment strategies for patients. Recently, strategies targeting extracellular matrix (ECM) components have gained attention. Fibrin is an ECM protein involved after MI. In this work, we constructed fibrin-targeted nanoparticles (NPs) by co-assembling a fibrin-targeted peptide (CREKA) and indocyanine green (ICG) and used them to enhance photoacoustic (PA) imaging for noninvasive detection of the infarct region to help diagnose MI.Methods: ICG NPs modified with CREKA were prepared (CREKA-ICG-LIP NPs). Then, the fundamental characteristics, stability, safety, and targeting ability of the NPs were detected. Finally, in an ischemia-reperfusion (IR) injury model, the performance of the NPs in detecting the infarct region in the model on PA imaging was evaluated.Results: CREKA-ICG-LIP NPs were successfully constructed and showed excellent basic characteristics, a high safety level, and an excellent targeting ability. After intravenous injection, the CREKA-ICG-LIP NPs accumulated in the injured region in the IR model. Then, the PA signal in the infarct region could be detected by the ultrasound transducer of the Vevo LAZR Photoacoustic Imaging System.Conclusion: This work provides new insights for non-invasive, real-time imaging techniques to detect the region of myocardial injury and help diagnose MI based on a PA imaging system with high sensitivity in optical imaging and deep penetration in ultrasound imaging.Keywords: PA imaging, MI, infarction region, diagnosis, CREKA, ICG

Long noncoding RNAs (lncRNAs) may serve as potential molecular diagnostic markers to improve the capacity of earlier and more accurate diagnosis of dilated cardiomyopathy (DCM). We integrated five independent transcriptomic datasets (

Background Ultrasonography is commonly used to diagnose left ventricular noncompaction (LVNC). A ratio of noncompacted to compacted myocardium (NC/C ratio) > >2 is often used to diagnose LVNC. However, a large proportion of patients with noncompact myocardium have NC/C Methods We included children diagnosed with LVNC between 0 and 15 years of age from January 2007 to December 2018. LVNC was diagnosed based on Stöllberger standard when over three trabeculae were found to be associated with the interventricular recesses. A maximal end systolic ratio of noncompacted to compacted layers was NC/C ratio. Outcomes for LVNC subjects with NC/C 2 were compared using Kaplan-Meier methods. Results There were 124 newly diagnosed LVNC cases, classified as isolated (i-LVNC, n = 47) or non-isolated (ni-LVNC, n = 77) LVNC and NC/C > 2 (n = 43) or n = 81). The median (interquartile range) follow-up duration was 12 (3–30) months for all patients and 16 (6–36) months for survivors. Sixteen patients with i-LVNC died during follow-up. Patients with i-LVNC and NC/C > 2 had worse survival than those with NC/C p = 0.022). Conclusions In conclusion, during a 12-month follow-up, patients with i-LVNC with NC/C 2, suggesting that the former could have a more active and routine lifestyle.

Background An increased prevalence of adolescent metabolic syndrome (MS) is associated with adulthood cardiovascular diseases. This study aimed to explore the potential relationship of quality of life (QoL) and personality traits with adolescent MS. Methods A total of 1961 participants from Chongqing with an average age of 11.68 years old from a cohort study established in 2014 and followed up through 2019 were included. QoL information, Eysenck’s personality questionnaire and MS components were collected. Results A higher QoL domain score of physical activity ability (PAA) was a protective factor for both MS and MS score (all P P P = 0.04) and MS score (P P ≤ 0.01). Conclusions QoL score and extraversion personality score were independent protective factors against both MS prevalence and MS score, suggesting that community intervention to improve the QoL and psychological health of children are essential.

To analyze the clinical characteristics and prognosis of children with anti-N-methyl-The clinical data of 42 cases of anti-NMDAR encephalitis at Department of Pediatrics, Second Xiangya Hospital, Central South University from January 2015 to March 2018 were collected. The clinical features and followed-up outcomes were analyzed retrospectively.There were 15 cases (35.7%) of males and 27 cases (64.3%) of females in 42 children, with a ratio of 1꞉1.8. They were aged from 4 months to 17 years, with an average of (9.20±4.66) years. The most common initial symptoms were seizures (47.6%, 20/42) and mental behavior disorder (35.7%, 15/42). During the course of the disease, 85.7% patients(36/42) had mental and behavior disorder, 85.7% patients (36/42) had epilepsy, 76.2% (32/42) had speech disorder, 66.7% patients (28/42) had dyskinesia, 66.7% patients (28/42) had the decreased level of consciousness, 61.9% patients (26/42) had autonomic instability, and 57.1% (24/42) patients had sleep disorder. All the children had positive antibody against NMDA receptor resistance encephalitis in cerebrospinal fluid. Head MRI showed the abnormal incidence was 50.0% (21/42), and the lesions involved in parietal lobe, frontal lobe, temporal lobe, occipital lobe, midbrain, thalamus, basal ganglia and optic nerve. There was a patient with optic nerve damage combined with myelin oligodendrocyte glycoprotein (MOG) antibody positive. Forty cases were examined by electroencephalogram (EEG), 92.5% cases (37/40) were abnormal, mainly showing diffuse slow waves, and δ brushes could be seen in severe cases. And there was 1 patient (2.4%) complicated with mesenteric teratoma. The mRS score (2.14±1.46) at discharge was significantly lower than the highest mRS score (3.88±1.38) during hospitalization (Seizures, mental and behavior disorder, dyskinesias, speech disorder and autonomic instability are common clinical manifestations of anti-NMDAR encephalitis in children. The effect of immunotherapy is significant, and the time to start immunotherapy and the severity of the disease are important factors affecting the prognosis. Anti-NMDAR encephalitis can be combined with other autoantibodies, but its clinical significance and mechanism need further study.

Ambient particles with a diameter of

Endothelial progenitor cells (EPCs) are important to tissue repair and regeneration especially after ischemic injury, and very heterogeneous in phenotypes and biological features. Reactive oxygen species are involved in regulating EPC number and function. N-acetylcysteine (NAC) inhibits ischemia-induced reactive oxygen species formation and promotes ischemic limb recovery. This study was to evaluate the effect of NAC on EPC subpopulations in bone marrow (BM) and blood in mice with limb ischemia. Limb ischemia was induced by femoral artery ligation in male C57BL/6 mice with or without NAC treatment. EPC subpopulations, intracellular reactive oxygen species production, cell proliferation and apoptosis in BM and blood cells were analyzed at baseline, day 3 (acute ischemia) and 21 (chronic) after ligation. c-Kit+/CD31+, Sca-1+/Flk-1+, CD34+/CD133+, and CD34+/Flk-1+ were used to define EPC subpopulations. Limb blood flow, function, muscle structure, and capillary density were evaluated with laser Doppler perfusion imaging, treadmill test, and immunohistochemistry, respectively, at day 3, 7, 14 and 21 post ischemia. Reactive oxygen species production in circulating and BM mononuclear cells and EPCs populations were significantly increased in BM and blood in mice with acute and chronic ischemia. NAC treatment effectively blocked ischemia-induced reactive oxygen species production in circulating and BM mononuclear cells, and selectively increased EPC population in circulation, not BM, with preserved proliferation in mice with chronic ischemia, and enhanced limb blood flow and function recovery, while preventing acute ischemia-induced increase in BM and circulating EPCs. These data demonstrated that NAC selectively enhanced circulating EPC population in mice with chronic limb ischemia.

Background: The MTUS1 gene encodes a microtubule-associated protein involved in multiple processes including cell polarity and microtubule balance during myocardial development. Aims: To investigate the association between a de novo c. 2617A->C mutation in MTUS1 (NM_001001924.2) and non-compaction of ventricular myocardium (NVM) and explore the potential mechanisms. Methods: A de novo mutation in MTUS1 was identified for a familial pedigree with NVM. Lentiviral vectors containing MTUS1 wild type or the mutation MTUS1 were constructed and co-infected into HEK-293 cells. MTUS1, Rac1/Cdc42, α-tubulin, α/β-tubulin, polarity protein (PAR6), and the morphology of daughter cells were measured by real-time PCR, Western blot, and immunofluorescence assays, respectively. Results: The lentiviral vectors were constructed successfully. Immunofluorescence assays revealed the fluorescence intensity of α-tubulin to be decreased and α/β-tubulin to be increased in the mutation MTUS1 group. The fluorescence intensity of PAR6 was higher and morphology of the daughter cells in the mutation group was different from the wild type group. The phosphorylation of Rac1/Cdc42 in the mutation group was significantly lower than in the wild type group. Conclusions: A de novo mutation in MTUS1 decreased the stability of microtubules and increased cell polarity via the Rac1/Cdc42 pathway, which may partly elucidate the mechanism underlying cellular protection in NVM.

Background Our previous studies have demonstrated that Ca2+ desensitizing catechin could correct diastolic dysfunction in experimental animals with restrictive cardiomyopathy. In this study, it is aimed to assess the effects of green tea extract catechin on cardiac function and other clinical features in pediatric patients with cardiomyopathies. Methods Twelve pediatric cardiomyopathy patients with diastolic dysfunction were enrolled for the study. Echocardiography, ECG, and laboratory tests were performed before and after the catechin administration for 12 months. Comparison has been made in these patients before and after the treatment with catechin. Next Generation Sequencing was conducted to find out the potential causative gene variants in all patients. Results A significant decrease of isovolumetric relaxation time (115 ± 46 vs 100 ± 42 ms, P = 0.047 at 6 months; 115 ± 46 vs 94 ± 30 ms, P = 0.033 at 12 months), an increase of left ventricle end diastolic volume (40 ± 28 vs 53 ± 28 ml, P = 0.028 at 6 months; 40 ± 28 vs 48 ± 33 ml, P = 0.011 at 12 months) and stroke volume (25 ± 16 vs 32 ± 17 ml, P = 0.022 at 6 months; 25 ± 16 vs 30 ± 17 ml, P = 0.021 at 12 months) were observed with echocardiography in these patients 6-month after the treatment with catechin. Ejection fraction, left ventricular wall thickness, biatrial dimension remained unchanged. No significant side effects were observed in the patients tested. Conclusions This study indicates that Ca2+ desensitizing green tea extract catechin, is helpful in correcting the impaired relaxation in pediatric cardiomyopathy patients with diastolic dysfunction. Electronic supplementary material The online version of this article (10.1186/s12929-019-0528-7) contains supplementary material, which is available to authorized users.

Background: Myhre syndrome (MS) is a very rare connective tissue disorder characterized by facial dysmorphism, thickened skin, muscular pseudohypertrophy and joint limitation. Developmental delay is common. But there are no reports of MS combined with moyamoya disease (MMD). Here, we present the first Chinese case of MS complicated with MMD. Case presentation: A 7-old-year girl presented with developmental disorder, short stature, brachydactyly, short stature, and intellectual deficiency with behavioral problems. We sequenced SMAD4 using exome sequencing and identified a denovo mutation (p.Ile500Thr) in the patient. In addition, The patient also had recurrent hemiplegia and seizures was diagnosed with definitive MMD by digital subtraction angiography (DSA) according to the diagnostic criteria. Conclusions: MMD has never been described in the individual with the clinical presentation of MS. we present an unusual association of MS with a typical moyamoya syndrome in a young girl who developed recurrent hemiplegia and seizure in an effort to explore whether MS may contribute to the MMD.

Down syndrome (DS), as a typical genomic aneuploidy, is a common cause of various birth defects, among which is congenital heart disease (CHD). 40–60% neonates with DS have some kinds of CHD. However, the molecular pathogenic mechanisms of DS associated CHD are still not fully understood. This review summarizes available studies on DS associated CHD from seven aspects so as to provide a crucial and updated overview of what we known so far in this domain. Keywords: Down syndrome, Congenital heart disease, Molecular mechanisms

Background: The MTUS1 gene encodes a microtubule-associated protein involved in multiple processes including cell polarity and microtubule balance during myocardial development. Aims: To investigate the association between a de novo c. 2617A->C mutation in MTUS1 (NM_001001924.2) and non-compaction of ventricular myocardium (NVM) and explore the potential mechanisms. Methods: A de novo mutation in MTUS1 was identified for a familial pedigree with NVM. Lentiviral vectors containing MTUS1 wild type or the mutation MTUS1 were constructed and co-infected into HEK-293 cells. MTUS1, Rac1/Cdc42, α-tubulin, α/β-tubulin, polarity protein (PAR6), and the morphology of daughter cells were measured by real-time PCR, Western blot, and immunofluorescence assays, respectively. Results: The lentiviral vectors were constructed successfully. Immunofluorescence assays revealed the fluorescence intensity of α-tubulin to be decreased and α/β-tubulin to be increased in the mutation MTUS1 group. The fluorescence intensity of PAR6 was higher and morphology of the daughter cells in the mutation group was different from the wild type group. The phosphorylation of Rac1/Cdc42 in the mutation group was significantly lower than in the wild type group. Conclusions: A de novo mutation in MTUS1 decreased the stability of microtubules and increased cell polarity via the Rac1/Cdc42 pathway, which may partly elucidate the mechanism underlying cellular protection in NVM.

Figure S1. Echocardiographic changes of cardiac parameters during the study period of 6 and 12 months. Figure S2. Levels of BNP during the study period. (DOCX 259 kb)

Table S1. Cardiac function observed with electrocardiography in patients before and after the catechin administration. Table S2. Parameters measured with echocardiography in HCM patients. Table S3. Parameters measured with echocardiography in RCM patients. Table S4. Cardiac markers and BNP analysis. Table S5. Hepatic and renal functions. Table S6. NYHA classification. (DOCX 28 kb)

Synthetic apolipoprotein A-I (apoA-I) mimetic peptide 5F exhibits anti-atherosclerotic ability with largely unknown mechanism(s). Bone marrow (BM)-derived endothelial progenitor cells (EPCs) play a critical role in vascular integrity and function. The objective of the present study was to evaluate the effect of 5F on endothelial differentiation of BM stem cells and related mechanisms. Murine BM multipotent adult progenitor cells (MAPCs) were induced to differentiate into endothelial cells in vitro with or without 5F. The expression of endothelial markers vWF, Flk-1 and CD31 was significantly increased in the cells treated with 5F with enhanced in vitro vascular tube formation and LDL uptake without significant changes on proliferation and stem cell maker Oct-4 expression. Phosphorylated ERK1/2, not Akt, was significantly increased in 5F-treated cells. Treatment of MAPCs with PD98059 or small interfering RNA against ERK2 substantially attenuated ERK1/2 phosphorylation, and effectively prevented 5F-induced enhancement of endothelial differentiation of MAPCs. In vivo studies revealed that 5F increased EPCs number in the BM in mice after acute hindlimb ischemia that was effectively prevented with PD98059 treatment. These data supported the conclusion that 5F promoted endothelial differentiation of MAPCs through activation of ERK1/2 signaling.

In this study, we investigated whether unique pathological characteristics exist in teratomas that can trigger autoimmune anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. We compared a case of retroperitoneal teratoma associated with anti-NMDAR encephalitis and four control cases. The encephalitis-positive case showed that (i) more dysplastic neuroglia with higher Ki-67 labeling index values than the control cases, which met the diagnostic criteria of astrocytoma, (ii) the NMDAR subunit NR1 was expressed more abundantly in neuroglial tissue where many neuroglial cells co-expressed glial fibrillary acidic protein (GFAP) and NR1 and formed abnormally large cellular masses, (iii) intense NR1 expression occurs in squamous epithelium near neuroglial tissue and lymphocyte infiltration. This study showed that dysplastic neuroglial tissue resembling central nervous system tumors, which might promote autoimmunity, distinguished the case with NMDAR encephalitis from the controls. Additionally, abnormal expression of NR1 occurs in non-neural tissues and could be triggered by inflammation and participate in autoimmunity.

Heart failure is a common, costly, and potentially fatal condition. The cardiac sarcoplasmic reticulum Ca-ATPase (SERCA2a) plays a critical role in the regulation of cardiac function. Previously, low SERCA2a expression was revealed in mice with heart failure. Epigallocatechin-3-gallate (EGCG) can function as an epigenetic regulator and has been reported to enhance cardiac function. However, the underlying epigenetic regulatory mechanism is still unclear. In this study, we investigated whether EGCG can up-regulate SERCA2a via histone acetylation and play role in preventing heart failure. For this, we generated a mouse model of heart failure by performing a minimally invasive transverse aortic constriction (TAC) operation and used this to test the effects of EGCG. The TAC+EGCG group showed nearly normal cardiac function compared to that in the SHAM group. The expression of SERCA2a was decreased at both the mRNA and protein levels in the TAC group but was enhanced in the TAC+EGCG group. Levels of AcH3 and AcH3K9 were determined to decrease near the promoter region of Atp2a2 (the gene encoding SERCA-2a) in the TAC group, but were elevated in the TAC+EGCG group. Meanwhile, HDAC1 activity and binding near the Atp2a2 promoter were increased in the TAC group but decreased with EGCG addition. Further, binding levels of GATA4 and Mef2c near the Atp2a2 promoter region were reduced in TAC hearts, which might have been caused by histone hypoacetylation; this was reversed by EGCG. Together, upregulation of SERCA2a via the modification of histone acetylation plays a role in EGCG-mediated prevention of pressure overload-induced heart failure, and this might represent a novel pharmacological target for the treatment of heart failure.

Cardiovascular disease remains a worldwide public health issue. As fructose consumption is dramatically increasing, it has been demonstrated that a fructose-rich intake would increase the risk of cardiovascular disease. In addition, emerging evidences suggest that low concentration alcohol intake may exert a protective effect on cardiovascular system. This study aimed to investigate whether low-concentration alcohol consumption would prevent the adverse effects on cardiovascular events induced by high fructose in mice. From the results of hematoxylin-eosin staining, echocardiography, heart weight/body weight ratio and the expression of hypertrophic marker ANP, we found high-fructose result in myocardial hypertrophy and the low-concentration alcohol consumption would prevent the cardiomyocyte hypertrophy from happening. In addition, we observed low-concentration alcohol consumption could inhibit mitochondria swollen induced by high-fructose. The elevated levels of glucose, triglyceride, total cholesterol in high-fructose group were reduced by low concentration alcohol. Low expression levels of SIRT1 and PPAR-γ induced by high-fructose were significantly elevated when fed with low-concentration alcohol. The histone lysine 9 acetylation (acH3K9) level was decreased in PPAR-γ promoter in high-fructose group but elevated when intake with low concentration alcohol. The binding levels of histone deacetylase SIRT1 were increased in the same region in high-fructose group, while the low concentration alcohol can prevent the increased binding levels. Overall, our study indicates that low-concentration alcohol consumption could inhibit high-fructose related myocardial hypertrophy, cardiac mitochondria damaged and disorders of glucose-lipid metabolism. Furthermore, these findings also provide new insights into histone acetylation-deacetylation mechanisms of low-concentration alcohol treatment that may contribute to the prevention of cardiovascular disease induced by high-fructose intake.

In order to make full use of wheat straw ash which is abundant and causes some serious environmental problems in the north of China, an environmentally friendly route is proposed to convert the wheat straw ash to useful materials in this paper. In this route, low surface area SiO2 microspheres are obtained from wheat straw ash, with the activated carbon and Nitrogen–Phosphorus–Potassium (NPK) compound fertilizer as by-products. KOH is used as the silica extraction reagent and H3PO4 is the precipitator. The resulting SiO2 microspheres with narrow size distribution have an amorphous structure with diameters of approximately 480 nm and a specific surface area of 47.79 m2 g−1 under the optimized synthesis conditions with a volume ratio of 1 : 1.5 : 1 for extract/water/ethanol, a pH value of 8 and H3PO4 solution dripping rate of 3 mL min−1. In this optimized route, the yields of SiO2 and activated carbon reach 96.77% and 71.89%, respectively. The waste water produced in this process is used to produce NPK compound fertilizer. The whole route is an environmentally friendly process without any emission of pollution.

Aims: Cardiomyopathies are common cardiovascular diseases in children. Cardiac magnetic resonance imaging (cMRI) and echocardiography (Echo) are routinely applied in the detection and diagnosis of pediatric cardiomyopathies. In this study, we compared and explored the correlation between these two measurements in pediatric patients with various cardiomyopathies. Methods and Results: A total of 53 pediatric patients with cardiomyopathy hospitalized during the recent 3 years in our hospital were analyzed. All of them and 22 normal controls were assessed by both cMRI and Echo. Cardiac function of the patients was graded according to the New York Heart Association functional classification. The cardiac function indexes measured with both cMRI and Echo included left-ventricular (LV) end-diastolic volume (EDV), end-systolic volume, ejection fraction and fractional shortening. These parameters were somehow lower in cMRI measurements than in Echo measurements. The index of diastolic function, such as peak filling rate (PFR) measured with cMRI, had a good correlation with the clinical cardiac functional score, while the index of the diastolic function (early/atrial filling ratio and isovolumic relaxation time) measured with Echo was not well correlated with the clinical cardiac function score. Significant systolic dysfunction was detected by cMRI in 34 patients with dilated cardiomyopathy, LV noncompaction or endocardial fibroelastosis. Significant diastolic dysfunction was detected by cMRI in 19 patients with hypertrophic cardiomyopathy or restrictive cardiomyopathy showing an alteration in PFR and EDV. Conclusion: Both cMRI and Echo are of great value in the diagnosis and assessment of cardiac function in pediatric patients with cardiomyopathy. cMRI could accurately display the characteristic morphological changes in the hearts affected with cardiomyopathies, and late gadolinium enhancement on cMRI may reveal myocardial fibrosis, which has obvious advantages over Echo measurements in diagnosis. Furthermore, cMRI can quantitatively determine ventricular function because it does not make invalid geometrical assumptions.

The authors thank the Engineering and Physical Sciences Research Council (EPSRC) for funding (EP/K036769/1; EP/K022237/1) and Royal society for a Wolfson Merit Award(JI). We have demonstrated that resorcinol–formaldehyde resin polymers are good visible light responsive photocatalysts, with band gap energies ranging from ca. 1.80 to 2.00 eV. They were found to be photoactive in terms of decomposition of organic substrates under visible light irradiation. The photocatalytic performance of resins could be markedly enhanced by coupling with electron conducting materials such as reduced graphene oxide. Photocatalytic water oxidation was also achievable on the hybrid reduced graphene oxide/resin catalyst with a sacrificial agent. These industrial widely-used resins exhibit many merits as photocatalysts such as low-cost, high surface area, large pore size and volume, facile preparation and scalability for development of eco-friendly commercial products with “self-cleaning” properties, based on their capability for the oxidative removal of organic pollutants under visible light. Postprint Publisher PDF

Early-onset epileptic encephalopathies (EOEEs) are clinically and genetically heterogeneous disorders characterized by intractable seizures and unremitting interictal paroxysmal epileptiform activity. Consequently, these syndromes impair neurodevelopment during the first year of life. Currently, the etiology of these disorders is largely unknown. In this study, Childhood-Onset Epilepsy Gene Panel Testing (containing 511 epilepsy-related genes) was performed in a parent-offspring trio. In this family, the son had refractory seizures, intellectual disability, and motor abnormalities, and he was diagnosed with EOEE. The boy later died from a sudden unexpected death in epilepsy (SUDEP) at the age of 26 months. In this case, we identified a de novo mutation (c.4423G > A; glycine [Gly]1475 arginine [Arg]) classified as heterozygous missense located in the inactivation gate section of the SCN8A (voltage-gated sodium-channel type VIII alpha subunit) gene. This result strengthens the association between the SCN8A gene and EOEE, and more attention should be given to its high rate of SUDEP. Further studies to determine the pathogenic mechanisms of SCN8A mutations should be warranted at the inactivation gate section of this sodium channel in both neurons and cardiac muscles.

Background Bone marrow derived stem cells (BMSCs) have the potential to differentiate into cardiomyocytes, but the rate of differentiation is low and the mechanism of differentiation is unclear completely. Here, we aimed to investigate the role of miR1-2 in differentiation of mouse BMSCs into cardiomyocyte-like cells and reveal the involved signaling pathways in the procedure. Methods Mouse BMSCs were treated with miR1-2 and 5-azacytine (5-aza). The expression of cardiac cell markers: NKx2.5, cTnI and GATA4 in BMSCs were examined by qPCR. The apoptosis rate was detected by flow cytometry and the activity of the Wnt/β-catenin signaling pathway was evaluated by measuring the upstream protein of this signaling pathway. Results After over-expression of miR1-2 in mouse BMSCs, the apoptosis rate was significantly lower than the 5-aza group, while the expressions of cardiac-specific genes: such as Nkx2.5, cTnI and GATA4 were significantly increased compared to the control group and the 5-aza group. Meanwhile, over-expression of miR1-2 in mouse BMSCs enhanced the expression of wnt11, JNK, β-catenin and TCF in the Wnt/β-catenin signaling pathway. Use of LGK-974, an inhibitor of Wnt/β-catenin signaling pathway, significantly reduced the expression of cardiac-specific genes and partially blocked the role of the miR1-2. Conclusion Over-expression of miR1-2 in mouse BMSCs can induce them toward promoted cardiomyocyte differentiation via the activation of the Wnt/β-catenin signaling pathway. Compared to 5-aza, miR1-2 can induce differentiation of BMSCs into cardiomyocytes more effectively with a less cytotoxicity.