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By fabricating patterned electrodes on a dumbbell‐shaped cavity semiconductor laser, the coherence of the laser can be switched by only changing the injection current. The threshold current and the peak power of the laser are 0.75 A and 1.41 W @ 3 A. Under the injection of small and large currents, the measured speckle contrasts are 40.0% @ 0.8 A and 7.0% @ 3 A. And the corresponding horizontal far‐field divergence angles are 4.05° and 8.7°, respectively, showing a high directionality. Such a laser with a wide range of adjustable coherence and a high directionality has a great potential in the field of bioimaging. [ABSTRACT FROM AUTHOR]

Background. Tumor microenvironment (TME) is closely related to the progression of glioma and the therapeutic effect of drugs on this cancer. The aim of this study was to develop a signature associated with the tumor immune microenvironment using machine learning. Methods. We downloaded the transcriptomic and clinical data of glioma patients from the Chinese Glioma Genome Atlas (CGGA) databases (mRNAseq_693). The single-sample Gene Set Enrichment Analysis (ssGSEA) database was used to quantify the relative abundance of immune cells. We divided patients into two different infiltration groups via unsupervised clustering analysis of immune cells and then selected differentially expressed genes (DEGs) between the two groups. Survival-related genes were determined using Cox regression analysis. We next randomly divided patients into a training set and a testing set at a ratio of 7 : 3. By integrating the DEGs into least absolute shrinkage and selection operator (LASSO) regression analysis in the training set, we were able to construct a 15-gene signature, which was validated in the testing and total sets. We further validated the signature in the mRNAseq_325 dataset of CGGA. Results. We identified 74 DEGs associated with tumor immune infiltration, 70 of which were significantly associated with overall survival (OS). An immune-related gene signature was established, consisting of 15 key genes: adenosine triphosphate (ATP)-binding cassette subfamily C member 3 (ABCC3), collagen type IV alpha 1 chain (COL4A1), podoplanin (PDPN), annexin A1 (ANXA1), COL4A2, insulin-like growth factor binding protein 2 (IGFBP2), serpin family A member 3 (SERPINA3), CXXC-type zinc finger protein 11 (CXXC11), junctophilin 3 (JPH3), secretogranin III (SCG3), secreted protein acidic and rich in cysteine (SPARC)-related modular calcium-binding protein 1 (SMOC1), Cluster of Differentiation 14 (CD14), COL1A1, S100 calcium-binding protein A4 (S100A4), and transforming growth factor beta 1 (TGF-β1). The OS of patients in the high-risk group was worse than that of patients in the low-risk group. GSEA showed that interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducer and activator of transcription (STAT3) signaling, interferon gamma (IFN-γ) response, angiogenesis, and coagulation were more highly enriched in the high-risk group and that oxidative phosphorylation was more highly enriched in the low-risk group. Conclusion. We constructed a stable gene signature associated with immune infiltration to predict the survival rates of glioma patients. [ABSTRACT FROM AUTHOR]

Summary: Root hair is regarded as a pivotal complementary survival tactic for mycorrhizal plant like Abies beshanzuensis when symbiosis is disrupted. Relatively little is known about the mechanism underlying root hair morphogenesis in plant species that are strongly dependent on mycorrhizal symbiosis. Many of these species are endangered, and this knowledge is critical for ensuring their survival.Here, a MYB6/bHLH13‐sucrose synthase 2 (AbSUS2) module was newly identified and characterized in A. beshanzuensis using bioinformatics, histochemistry, molecular biology, and transgenesis.Functional, expression pattern, and localization analysis showed that AbSUS2 participated in sucrose synthesis and was involved in root hair initiation in A. beshanzuensis. Additionally, the major enzymatic product of AbSUS2 was found to suppress root hair initiation in vitro. Our data further showed that a complex involving the transcription factors AbMYB6 and AbbHLH13 directly interacted with the promoter of AbSUS2 and strengthened its expression, thereby inhibiting root hair initiation in response to exogenous sucrose.Our findings offer novel insights into how root hair morphogenesis is regulated in mycorrhizal plants and also provide a new strategy for the preservation of endangered mycorrhizal plant species. [ABSTRACT FROM AUTHOR]

Abstract: In this study, TiO2 nanotube arrays (TiO2-NTs) with various intertube spaces were fabricated in the electrolyte with different water contents and the CdS nanoparticles (CdS NPs) were further deposited onto the TiO2-NTs as a sensitizer via a sequential chemical bath deposition (S-CBD) method. The FE-SEM, TEM, XRD and XPS results demonstrated that the CdS NPs were uniformly deposited onto the surface of TiO2-NTs. It was found that higher water content in electrolyte was in favor of large intertube space and pore size and the uniform deposition of CdS NPs. The photocatalytic degradation of methyl orange was tested with the as-prepared CdS/TiO2-NTs under visible light (λ>400nm). It was found that the photodegradation rate reached as high as 96.7% under visible irradiation for 180min. In addition, a reasonable degradation rate of 75.8% was achieved even after 5 cycles, suggesting a good photocatalytic stability of the as-prepared CdS/TiO2-NTs. [Copyright &y& Elsevier]

The central nervous system (CNS) is the most delicate system in human body, with the most complex structure and function. It is vulnerable to trauma, infection, neurodegeneration and autoimmune diseases, and activates the immune system. An appropriate inflammatory response contributes to defence against invading microbes, whereas an excessive inflammatory response can aggravate tissue damage. The NLRP3 inflammasome was the first one studied in the brain. Once primed and activated, it completes the assembly of inflammasome (sensor NLRP3, adaptor ASC, and effector caspase-1), leading to caspase-1 activation and increased release of downstream inflammatory cytokines, as well as to pyroptosis. Cumulative studies have confirmed that NLRP3 plays an important role in regulating innate immunity and autoimmune diseases, and its inhibitors have shown good efficacy in animal models of various inflammatory diseases. In this review, we will briefly discuss the biological characteristics of NLRP3 inflammasome, summarize the recent advances and clinical impact of the NLRP3 inflammasome in infectious, inflammatory, immune, degenerative, genetic, and vascular diseases of CNS, and discuss the potential and challenges of NLRP3 as a therapeutic target for CNS diseases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cardiomyopathy (CM) is a heterogeneous group of myocardial diseases in children. This study aimed to identify demographic features, clinical presentation and prognosis of children with CM. Clinical characteristics and prognostic factors associated with mortality were evaluated by Cox proportional hazards regression analyses. Genetic testing was also conducted on a portion of patients. Among the 317 patients, 40.1%, 25.2%, 24.6% and 10.1% were diagnosed with dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), left ventricular noncompaction cardiomyopathy (LVNC) and restrictive cardiomyopathy (RCM), respectively. The most common symptom observed was dyspnea (84.2%). Except for HCM, the majority of patients were classified as NYHA/Ross class III or IV. The five-year survival rates were 75.5%, 67.3%, 74.1% and 51.1% in DCM, HCM, LVNC and RCM, respectively. The ten-year survival rates were 60.1%, 56.1%, 57.2% and 41.3% in DCM, HCM, LVNC and RCM, respectively. Survival was inversely related to NYHA/Ross class III or IV in patients with DCM, HCM and RCM. Out of 42 patients, 32 were reported to carry gene mutations. Conclusions: This study demonstrates that CM, especially RCM, is related to a high incidence of death. NYHA/Ross class III or IV is a predictor of mortality in the patients and gene mutations may be a common cause. Trial registration: MR-50-23-011798. What is Known: • Cardiomyopathy (CM) is a heterogeneous group of myocardial diseases and one of the leading causes of heart failure in children due to the lack of effective treatments. • There remains scarce data on Asian pediatric populations though emerging studies have assessed the clinical characteristics and outcomes of CM. What is New: • A retrospective study was conducted and the follow-up records were established to investigate the clinical characteristics, the profile of gene mutations and prognostic outcomes of children with CM in Western China. • CM, especially RCM, is related to a high incidence of death. NYHA/Ross class III or IV is a predictor of mortality in the patients and gene mutations may be a common cause. [ABSTRACT FROM AUTHOR]

Background: Continuous nitrogen (N) deposition interferes with soil N cycling in forests, which highly impacts soil nitrous oxide (N2O) emissions and accelerates global warming. Chinese fir (Cunninghamia lanceolata (Lamb.) Hook) is one of the most widely planted species in southern China, and is usually located in areas with high N deposition rates. However, the impact of N deposition on soil N2O emissions in subtropical Chinese fir plantations and the potential risk of increasing N input remain elusive. Methods: Here, we conducted an in situ study in a subtropical Chinese fir plantation at Fengyang Mountain Nature Reserve, China, from 2019 to 2020 with four N addition rates: 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). Results: We found that soil N2O emission rates increased with N addition rates by 71%, 176%, and 241% under LN, MN, and HN treatment compared to CK, respectively, and reached a significant level only under HN. Soil moisture was significantly reduced together with increased leaf N concentrations under N addition. Meanwhile, the microbial biomass in the middle of the growing season was significantly lower than at the end of the growing season. These results may suggest that N deposition stimulated plants to take up more N and water, which intensified plant-microbe competition and therefore alleviated further increases in N2O emissions under N deposition, especially under low N inputs. N deposition enhanced the abundance of ammonia oxidizing archaea and bacteria and the accumulation of NO3−-N in the soil but did not affect the abundance of nitrate-reducing bacteria (nirS and nirK). The results likely support that nitrification processes act as the major source of enhanced N2O emissions under N fertilization. Conclusions: Our study advances our understanding of the impacts of N deposition on the soil N2O emissions in the Chinese fir plantations and highlights that plant N acquisition needs to be incorporated as an important explanatory variable when predicting N2O fluxes under global increases in N deposition. [ABSTRACT FROM AUTHOR]

ADV and US imaging of IMTP-Fe 3 O 4 NPs at different intensities of LIFU irritation and different time in vitro. Correction: A non-invasive nanoparticles for multimodal imaging of ischemic myocardium in rats 5 Phase transition and US imaging in vitro. a Light microscope images of phase transformation induced by LIFU (scale bar = 10 m). b The ultrasound imaging (left: B-Mode, right: CEUS) of IMTP-Fe3O4-PFH NPs with time- and intensity-dependent ADV. Quantitative analysis of the echo intensity of NPs after LIFU irradiation at different intensities and time in B-mode (c) and CEUS-mode (d) Supplementary Information Graph: Additional file 1: Figure S7. [Extracted from the article]

Alcohol abuse during pregnancy may cause fetal cardiac developmental abnormalities. Our previous studies showed that alcohol could induce histone hyperacetylation and over-expression of cardiac transcription factors both in vivo and in vitro. The objective of the present study was to investigate the role of ERK1/2 signaling pathway in alcohol-induced histone hyperacetylation and up-regulation of cardiac transcription factors in H9c2 cells. The Cardiac cell line H9c2 was cultured with alcohol. U0126, a specific inhibitor of ERK1/2 pathway was employed to block the ERK1/2 signaling pathway. Western blotting analysis showed that alcohol significantly enhanced the levels of phosphorylated ERK1/2 and induced hyperacetylation of histone3, which were both effectively prevented with U0126. Real-time PCR showed that U0126 treatment significantly decreased alcohol-induced over-expression of GATA4 and MEF2c, and the basal expression level of GATA4, but did not affect MEF2c. ChIP assay showed that U0126 treatment significantly decreased alcohol-induced hyperacetylation of histone3 near the promoter regions of GATA4 and MEF2c. The basal acetylation level of histone3 near the promoter region of GATA4 was affected by U0126 as well, but not that near the promoter region of MEF2c. These data indicated that ERK1/2 signaling played an important role in mediating alcohol induced over-expression of GATA4 and MEF2c, which is possibly through the up-regulation of acetylation of histone3 near the gene promoters that affects the expression of GATA4 and MEF2c in H9c2 cells. ERK1/2 pathway might be a potential target for the intervention of alcohol induced congenital heart diseases. [ABSTRACT FROM AUTHOR]

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. • Delayed diagnosis of congenital heart disease (CHD) can lead to a series of irreversible complications. • RCRnet model can preliminarily identify specific types of left-to-right shunt CHD and improve screening detection rate. • The diagnostic effect of RCRnet model is better than that of many experienced cardiovascular physicians. [ABSTRACT FROM AUTHOR]

A novel glucose biosensor based on graphene nanosheets (GNs) modified gold nanowire arrays (AuNWAs) electrode was constructed. Highly ordered gold nanowire arrays were prepared by direct electrodeposition in anodic aluminum oxide templates. GNs were synthesized through a public route involving graphite oxidation, exfoliation, and chemical reduction. Field emission scanning electron microscope and high-resolution transmission electron microscope were employed to characterize the as-prepared AuNWAs and GNs. Glucose oxidase was immobilized on the surface of GNs-AuNWAs modified electrode via a cross-linking method. The cyclic voltammetry results showed that the GNs-AuNWAs-based glucose biosensors have high catalysis activity to hydrogen peroxide (HO) than those modified with GNs or AuNWAs only. Furthermore, amperometric response was employed to detect glucose concentration owing to its simplicity, high selectivity, and relative low cost. Glucose biosensors based on GNs-AuNWAs showed excellent performance with high sensitivity of 40.25 μA cm (mmol/L), low detection limit of 0.02 mmol/L, and a linear range from 0.02 to 3 mmol/L. [ABSTRACT FROM AUTHOR]

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 < 0.01), which was mainly negatively correlated with the MS components of central obesity, diastolic blood pressure (DBP) and triglyceride levels, as well as positively correlated with high density lipoprotein cholesterol (HDL-C) level. The total QoL score was negatively correlated with triglyceride levels and positively correlated with DBP (all P < 0.01). High extraversion personality score was a protective factor against adolescent MS (P = 0.04) and MS score (P < 0.05), which were mainly negatively correlated with the MS components of waist circumference, systolic blood pressure and TGs, and positively correlated with HDL-C (all 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. [ABSTRACT FROM AUTHOR]

Air injection is an accessory technique during scleral buckling (SB). Subclinical subretinal fluid (SRF) may presence and persistent after SB. The impact of air injection on SRF is unclear. In the study, we retrospectively enrolled 51 patients with macular-involving RD who had undergone successful SB. They were categorized into Group A (SB without air injection) and Group B (SB with air injection). First, we found that although group B seem to be severer than group A before surgery, Kaplan–Meier graph showed that SRF absorbed more rapidly in group B after surgery, and the incidence of SRF in group B was much lower during the whole follow-up period. Moreover, the cases with superior breaks had the lowest incidence. Second, during the follow-up period, there was no significant difference about postoperative complication between two groups. Lastly, risk factors for persistent SRF were investigated with binary logistic regression, and no risk factor was found. In conclusion, air injection during the SB might accelerate SRF absorption and reduce the incidence of persistent SRF, especially for the longstanding macular-off RD with superior breaks. [ABSTRACT FROM AUTHOR]

Background: Ischemic heart disease (IHD) is the leading cause of morbidity and mortality worldwide, and imposes a serious economic load. Thus, it is crucial to perform a timely and accurate diagnosis and monitoring in the early stage of myocardial ischemia. Currently, nanoparticles (NPs) have emerged as promising tools for multimodal imaging, because of their advantages of non-invasion, high-safety, and real-time dynamic imaging, providing valuable information for the diagnosis of heart diseases. Results: In this study, we prepared a targeted nanoprobe (termed IMTP-Fe3O4-PFH NPs) with enhanced ultrasound (US), photoacoustic (PA), and magnetic resonance (MR) performance for direct and non-invasive visual imaging of ischemic myocardium in a rat model. This successfully designed nanoprobe had excellent properties such as nanoscale size, good stability, phase transformation by acoustic droplet vaporization (ADV), and favorable safety profile. Besides, it realized obvious targeting performance toward hypoxia-injured cells as well as model rat hearts. After injection of NPs through the tail vein of model rats, in vivo imaging results showed a significantly enhanced US/PA/MR signal, well indicating the remarkable feasibility of nanoprobe to distinguish the ischemic myocardium. Conclusions: IMTP-Fe3O4-PFH NPs may be a promising nanoplatform for early detection of ischemic myocardium and targeted treatment under visualization for the future. [ABSTRACT FROM AUTHOR]

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 (n = 504) from Gene Expression Omnibus for systematic identification of lncRNA-based diagnostic biomarkers in DCM. The multivariate logistic regression model based on the six lncRNAs (AC016722.3, AL589986.2, AC006007.1, AC092687.3, GS1-124K5.4, and AC007126.1) in the ceRNA networks showed high sensitivity and specificity (area under curves >0.8, p < 0.0001) of DCM diagnosis in the training and validation datasets. Functional analysis revealed that the autophagy, protein acetyltransferase, and DNA polymerase activity were associated with high levels of the six-lncRNA signature, while the collagen trimer, extracellular matrix structural constituent, and MHC protein complex were associated with low levels of the signature. Pathway analysis showed that high levels of the six-lncRNA signature were associated with upregulated selective autophagy, interleukin 17 signalings, and extracellular matrix interactions, while were associated with downregulated extracellular matrix organization and collagen formation. The identified six-lncRNA signature, with high performance in molecular diagnosis of DCM, might be applied in future clinical practices combined with traditional markers. [ABSTRACT FROM AUTHOR]

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. • Special pathologic change existed in teratomas of anti-NMDAR encephalitis patients. • Dysplastic neuroglia was found resembling CNS tumors with higher NR1 expression. • Intense NR1 expressed in squamous cells near neuroglia and lymphocyte infiltration. • Dysplastic neuroglia might induce autoimmunity for anti-NMDAR encephalitis. • Inflammation may raise non-neural tissues' NR1 expression affecting autoimmunity. [ABSTRACT FROM AUTHOR]

Apoptosis of vascular smooth muscle cells (VSMCs) is a process that regulates vessel remodeling in various cardiovascular diseases. The specific mechanisms that control VSMC apoptosis remain unclear. The present study aimed to investigate whether microRNA-494 (miR-494) is involved in regulating VSMC apoptosis and its underlying mechanisms. Cell death ELISA and terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assays were used to detect apoptosis of murine VSMCs following stimulation with tumor necrosis factor-α (TNF-α). The results indicated that TNF-α upregulated VSMC apoptosis in a dose-dependent manner. Microarray analysis was used to evaluate the expression profile of microRNAs following TNF-α stimulation in murine VSMCs. The expression of miR-494 was downregulated, whereas B-cell lymphoma-2-like 11 (BCL2L11) protein expression levels were upregulated in VSMCs following treatment with TNF-α. Luciferase reporter assays confirmed that BCL2L11 was a direct target of miR-494. Transfection with miR-494 mimics decreased VSMC apoptosis and downregulated BCL2L11 protein levels. Conversely, transfection with miR-494 inhibitors increased cell apoptosis and upregulated BCL2L11 protein levels, suggesting that miR-494 may function as an essential regulator of BCL2L11. The increase in apoptosis caused by miR-494 inhibitors was abolished in cells co-transfected with BCL2L11-targeting small interfering RNA. The findings of the present study revealed that miR-494 inhibited TNF-α-induced VSMC apoptosis by downregulating the expression of BCL2L11. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Abusive alcohol utilization of pregnant woman may cause congenital heart disease ( CHD) of fetus, where alcohol ignites histone H3 hyperacetylation leading to abnormal development of heart morphogenesis and associated genes. Knowledge about the regularized upstream genes is little, but bone morphogenetic protein ( BMP) signaling may actively and prominently take part in alteration in acetylation of histone H3. The supreme objective of this study was to unearth the involvement of BMP signaling pathway in alcohol-driven hyperacetylation of histone H3 in cardiomyoblast cells. Methods Cardiomyoblast cells (H9c2 cells) were addicted with alcohol (100 mM) for 24 hours. Dorsomorphin (5 μM) was used for the inhibition of BMP signaling pathway. We detected the phosphorylation activity of SMAD1/5/8, mRNA expression, histone acetyltransferases ( HAT)/histone deacetylase ( HDAC) activity, and acetylation of histone H3. Results Following alcohol exposure, phosphorylation of SMAD1/5/8 and HAT activities was increased to a significant extent, while histone H3 acetylation and expression of heart development-related genes were also increased. The said phenomenon influenced by alcohol was reverted upon dorsomorphin treatment to the cells without effecting HDAC activity. Conclusions The data clearly identified that BMP-mediated histone H3 acetylation of heart development-related genes might be one of the possible cellular mechanisms to control alcohol-induced expression of heart development-related genes. Dorsomorphin, on the other hand, may modulate alcohol-induced hyperacetylation of histone H3 through BMP targeting, which could be a potential way to block CHD. [ABSTRACT FROM AUTHOR]

Background: Recurrent convulsions can cause irreversible astrocyte death, impede neuron regeneration, and further aggravate brain damage. MicroRNAs have been revealed as players in the progression of numerous diseases including cancer and Alzheimer's disease. Particularly, microRNA has been found linked to seizure-induced neuronal death. In this study, a rat model of recurrent convulsions induced by flurothyl treatments was utilised to assess the alterations of microRNA expressions in hippocampus tissues. We also applied an in vitro model in which primary astrocytes were exposed to kainic acid to verify the targets of miR-34b-5p identified in the animal model.Results: We discovered that miR-34b-5p, a member of the miR-34 family, increased significantly in flurothyl-treated rat hippocampus tissue. More surprisingly, this upregulation occurred concurrently with accumulating astrocyte apoptosis, indicating the involvement of miR-34b-5p in seizures caused astrocyte apoptosis. Results from the in vitro experiments further demonstrated that miR-34b-5p directly targeted Bcl-2 mRNA, translationally repressed Bcl-2 protein, and thus modulated cell apoptosis by influencing Bcl-2, Bax, and Caspase-3.Conclusion: Our findings prove microRNAs play a role in mediating recurrent convulsions-induced astrocyte death and further indicate that miR-34b-5p could acts as a regulator for astrocyte apoptosis induced by recurrent seizures. [ABSTRACT FROM AUTHOR]

Low-density lipoprotein (LDL) is non-atherogenic, while oxidized LDL (ox-LDL) is critical to atherosclerosis. N-acetylcysteine (NAC) has anti-atherosclerotic effect with largely unknown mechanisms. The present study aimed to determine if NAC could attenuate in vivo LDL oxidation and inhibit atherosclerosis. A single dose of human native LDL was injected intravenously into male C57BL/6 mice with and without NAC treatment. Serum human ox-LDL was detected 30 min after injection, reached the peak in 3 hours, and became undetectable in 12 hours. NAC treatment significantly reduced serum ox-LDL level without detectable serum ox-LDL 6 hours after LDL injection. No difference in ox-LDL clearance was observed in NAC-treated animals. NAC treatment also significantly decreased serum ox-LDL level in patients with coronary artery diseases and hyperlipidemia without effect on LDL level. Intracellular and extracellular reactive oxidative species (ROS) production was significantly increased in the animals treated with native LDL, or ox-LDL and in hyperlipidemic LDL receptor knockout (LDLR−/−) mice that was effectively prevented with NAC treatment. NAC also significantly reduced atherosclerotic plaque formation in hyperlipidemic LDLR−/− mice. NAC attenuated in vivo oxidation of native LDL and ROS formation from ox-LDL associated with decreased atherosclerotic plaque formation in hyperlipidemia. [ABSTRACT FROM AUTHOR]

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. • EGCG had a protective effect on pressure overload-induced cardiac dysfunction by affecting energy metabolism. • EGCG ameliorated myocardial hypertrophy and fibrosis caused by pressure overload. • Proteomics was used to explore the cardioprotective effects of EGCG. [ABSTRACT FROM AUTHOR]

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. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims The present study was to investigate the effect of hydrogen peroxide (H 2 O 2 ) on bone marrow stem cells and their endothelial differentiation and the underlying mechanisms in vitro. Main methods Rat bone marrow multipotent adult progenitor cells (MAPCs) were used as the source of bone marrow stem cells, and treated with H 2 O 2 (with the final concentration from 0 to 50 μM) with or without N-acetylcysteine (NAC, 0.1 mM). Reactive oxygen species (ROS) was measured by electron paramagnetic resonance (EPR) and fluorescent microscope. Flow cytometry and immunoblotting were used to determine apoptosis and differentiation of MAPCs. Key findings H 2 O 2 generated a significant amount of intracellular and extracellular ROS in the culture system, substantially inhibited the proliferation of MAPCs and Oct-4 expression, and induced their apoptosis in a dose-dependent manner. Exposure to H 2 O 2 also significantly attenuated the endothelial differentiation of MAPCs with reduced expression of endothelial markers CD31 and FLK-1 as well as impaired in vitro vascular structure formation. Both intracellular and extracellular ROS production from H 2 O 2 were blocked by NAC. NAC treatment effectively prevented H 2 O 2 -induced reduction of Oct-4 expression in the cells. However, NAC treatment only partially prevented H 2 O 2 -induced apoptosis, and inhibition of cell proliferation and endothelial differentiation of MAPCs. Significance H 2 O 2 exposure suppressed Oct-4 expression in MAPCs through ROS-dependent mechanism, while increasing the apoptosis of MAPCs and inhibiting their proliferation and endothelial differentiation with a mechanism partially due to ROS generation in vitro. [ABSTRACT FROM AUTHOR]

TiO nanotube arrays (NTAs) with different intertube spaces were fabricated via electrochemical anodization process in the electrolyte with different water contents. Uniform distributed cadmium selenide (CdSe) nanoparticles were deposited onto the TiO NTAs through electrodeposition method. The influence of water contents in electrolyte on the microstructure and photocatalytic property of CdSe/TiO NTAs were studied. The results show that increasing the water content in electrolyte from 2 to 12 vol% can enlarge the intertube space from 0 to 22 nm, which is beneficial for the deposition of CdSe nanoparticles. The photocatalytic activity of CdSe/TiO NTAs was evaluated by measuring the degradation of methyl orange solutions under visible light. When water content was 10 vol%, CdSe nanoparticles distributed uniformly on the inner and outer surface of TiO NTAs. The photocatalytic tests indicated that CdSe/TiO NTAs composites exhibits excellent photocatalytic properties after visible light irradiation for 2 h, the degradation rate reached from 55.7 to 94.5 % when water content increased from 2 to 10 vol%, whereas the degradation rate of the TiO NTAs without CdSe modification is just 4.8 %. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: Highly ordered TiO2 nanotube arrays (NTAs) were fabricated on titanium substrate via electrochemical anodization method. CdSe nanoparticles were deposited on the TiO2 NTAs through the electrodeposition process. The influence of electrolyte concentration and deposition time on the visible light photocatalytic performance of CdSe/TiO2 NTAs was studied systematically. The photocatalytic activity of as-prepared samples was evaluated by degradation of methyl orange under visible light irradiation. The results indicated that the CdSe nanoparticles distributed uniformly on the surface of TiO2 NTAs when deposited in the electrolyte containing 0.02M CdCl2, 2mM SeO2 and 0.02M Na2SO4 with time of 600s. After irradiation under visible light for 2h, the degradation rate of CdSe/TiO2 NTAs composite material reached 94.4%, while the degradation rate of unmodified TiO2 NTAs was only 6.2 % under the same condition, demonstrating that the CdSe/TiO2 NTAs exhibited higher photocatalytic activity in visible light region. In addition, a reasonable degradation rate of 80.96% was achieved even after being used for 5 times. [Copyright &y& Elsevier]

Homogeneously dispersed silver nanoparticles (AgNPs) were successfully decorated onto the surface of TiO2 nanotube arrays (TNTA) by means of an in situ photoreduction method. TNTA films as supports exhibit excellent properties to prevent agglomeration of AgNPs, and they also avoid using polymer ligands, which is deleterious to enhancing the properties of the fabricated NPs. The silver particle size and its content could be controlled just by changing the immersion time. Detailed SEM and TEM analyses combined with energy-dispersive X-ray spectroscopy analyses with different immersion times (5, 10, 30, 60 min) have revealed the variation tendency. The prepared Ag/TNTA composite films were also characterized by XRD, , and high-resolution TEM. The UV/Vis spectra displayed a redshift of the absorption peak with the growth of AgNPs. The photocurrent response and the photoelectrocatalytic degradation of methyl orange (MO) were used to evaluate the photoelectrochemical properties of the fabricated samples. The results showed that the photocurrent response and photoelectrocatalytic activity largely depended on the loaded Ag particle size and content. TNTA films with a diameter of 17.92 nm and silver content of 1.15 at % showed the highest photocurrent response and degradation rate of MO. The enhanced properties could be attributed to the synergistic effect between AgNPs and TiO2. To make good use of this effect, particle size and silver content should be well controlled to develop the electron charge and discharge process during the photoelectrical process. Neither smaller nor larger AgNPs caused decreased photoelectrical properties. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

One of the most challenging issues in HIV-associated neurocognitive disorders (HAND) caused by HIV-1 virotoxins and drug abuse is the lack of understanding the underlying mechanisms that are commonly associated with disorders of the blood-brain barrier (BBB), which mainly consists of brain microvascular endothelial cells (BMEC). Here, we hypothesized that Glycoprotein 120 (gp120), methamphetamine (METH) and nicotine (NT) can enhance amyloid-beta (Aβ) accumulation in BMEC through Alpha7 nicotinic acetylcholine receptor (α7 nAChR). Both in vitro (human BMEC) (HBMEC) and in vivo (mice) models of BBB were used to dissect the role of α7 nAChR in up-regulation of Aβ induced by gp120, METH and NT. Aβ release from and transport across HBMEC were significantly increased by these factors. Methyllycaconitine (MLA), an antagonist of α7 nAChR, could efficiently block these pathogenic effects. Furthermore, our animal data showed that these factors could significantly increase the levels of Aβ, Tau and Ubiquitin C-Terminal Hydrolase L1 (UCHL1) in mouse cerebrospinal fluid (CSF) and Aβ in the mouse brains. These pathogenicities were significantly reduced by MLA, suggesting that α7 nAChR may play an important role in neuropathology caused by gp120, METH and NT, which are the major pathogenic factors contributing to the pathogenesis of HAND. [ABSTRACT FROM AUTHOR]