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Cardiomyopathy is a severe cardiac condition characterized by complex immune regulatory mechanisms. While the role of immune genes is recognized, the specifics of their regulation in cardiomyopathy are not fully understood. Recent studies highlight the significance of transposable elements (TEs) in various diseases, particularly their potential to modulate immune responses. This paper utilizes publicly available databases to explore the role of TEs in myocarditis: RNA Seq data and single-cell sequencing data were analyzed, with a focus on the mouse model of experimental autoimmune myocarditis (EAM). The RNA-Seq analysis revealed substantial upregulation of a range of immune genes in cardiac tissue. Further investigation using single-cell sequencing of cardiac immune cells identified specific expression of certain transposable elements (TEs) across different types of immune cells in the heart. Additionally, there was an overall increase in the expression of the ERVB7-1. LTR-MM transposon across various cells in the EAM model, suggesting a widespread impact of this transposon on the immune response in this disease context. The findings of this study highlight the intricate interplay between transposable elements and the immune system in cardiomyopathy, providing new insights into the molecular mechanisms underlying this condition. The discovery of specific TEs expression in cardiac immune cells and the overall increase in ERVB7-1. LTR-MM expression across the EAM model underscore the potential of these elements in modulating immune responses and contribute to our understanding of cardiomyopathy's pathogenesis. These observations open avenues for further research into the role of TEs in cardiac disases and may lead to novel therapeutic strategies.

[Introduction] The purpose of this paper is to research and analyze the influence of water resources on the development of the green hydrogen industry in China, reveal the contradiction between water resources and the development of green hydrogen industry, analyze the future development trend of the green hydrogen industry and to provide useful reference for the development layout of renewable energy hydrogen production projects in China. [Method] In order to prove that water resources could limit the development of the green hydrogen industry in "Northeast China, North China, Northwest China" and other areas, the analysis and the demonstration were made based on the field investigations and the documentary materials, considering water resources policies, water usage in traditional chemical industries, and hydrogen production technologies. [Result] The analysis results show that under the restriction of China's water resources-related policies, the layout of green hydrogen industry should consider the constraints of water resources, and the large-scale production of green hydrogen and its substitution for fossil energy hydrogen production cannot effectively save water. Instead, it may lead to an increase in water consumption by the chemical industry. Under the constraint of water resources, the development of China's green hydrogen industry must consider the layout from a holistic perspective, fully integrate the development trend of the existing chemical industry, and consider the abundant resources available such as seawater. [Conclusion] The development of the green hydrogen industry in China should not ignore the problems of existing policy framework, technology level, industrial layout and characteristics of existing resources. When arranging the layout of the green hydrogen projects, the current situation and future trends should be fully considered, and the problems posed by water resources on the green hydrogen industry should be solved from the perspective of the overall planning, the coordinated industrial development and the effective utilization of resources.

Summary: Prader-Willi syndrome (PWS) is a genetic disorder characterized by behavioral disturbances, hyperphagia, and intellectual disability. Several surveys indicate that PWS is also associated with cardiac abnormalities, possibly contributing to a high incidence of sudden death. However, the pathological mechanisms underlying cardiac dysfunction in PWS remain unclear. In this study, we found that deficiency in necdin, an intronless gene within PWS region, led to heart systolic and diastolic dysfunction in mice. Through yeast two-hybrid screening, we identified an interaction between necdin and non-muscle myosin regulatory light chain 12a/b (MYL12 A/B). We further showed that necdin stabilized MYL12 A/B via SGT1-heat shock protein 90 (HSP90) chaperone machinery. The zebrafish lacking the MYL12 A/B analog, MYL12.1, exhibited impaired heart function, while cardiac-specific overexpression of MYL12A normalized the heart dysfunction in necdin-deficient mice. Our findings revealed necdin dysfunction as a contributing factor to cardiomyopathy in PWS patients and emphasized the importance of HSP90 chaperone machinery and non-muscle myosin in heart fitness.

Pygopus (Pygo) has been identified as a specific nuclear co-activator of the canonical Wingless (Wg)/Wnt signaling pathway in Drosophila melanogaster. Pygo proteins consist of two conserved domains: an N-terminal homologous domain (NHD) and a C-terminal plant homologous domain (PHD). The PHD’s ability to bind to di- and trimethylated lysine 4 of histone H3 (H3K4me2/3) appears to be independent of Wnt signaling. There is ongoing debate regarding the significance of Pygo’s histone-binding capacity. Drosophila Pygo orthologs have a tryptophan (W) > phenylalanine (F) substitution in their histone pocket-divider compared to vertebrates, leading to reduced histone affinity. In this research, we utilized CRISPR/Cas9 technology to introduce the Pygo-F773W point mutation in Drosophila, successfully establishing a viable homozygous Pygo mutant line for the first time. Adult mutant flies displayed noticeable abnormalities in reproduction, locomotion, heart function, and lifespan. RNA-seq and cluster analysis indicated that the mutation primarily affected pathways related to immunity, metabolism, and posttranslational modification in adult flies rather than the Wnt signaling pathway. Additionally, a reduction in H3K9 acetylation levels during the embryonic stage was observed in the mutant strains. These findings support the notion that Pygo plays a wider role in chromatin remodeling, with its involvement in Wnt signaling representing only a specific aspect of its chromatin-related functions.

In harsh battlefield environments, tanks have to encounter some nonlinear characteristics including frictional moment, gear backlash and parameter drifts, etc. The existence of such nonlinear characteristics makes the controller design of tank gun control systems (TGCSs) challenging. In this paper, a barrier neuroadaptive control approach is proposed to handle the uncertainties and nonlinearities, so as to achieve satisfactory tracking performance for TGCSs. With a time-varying barrier Lyapunov function employed in controller design, the output error of TGCS is restricted within the preset bound during the control process. A radial basis function (RBF) neural network is built to approximate the uncertainties in tank gun control systems. An anti-windup control strategy is developed to deal with the input saturation nonlinearity, with a Nussbaum function used to compensate for the nonlinear term arising from input saturation. By reasonably applying filtering error into output-constrained adaptive backstepping control design, the three steps in the traditional backstepping control design are reduced to two steps. The asymptotic stability of the closed-loop TGCSs is proven by Lyapunov theory. Finally, a simulation example is presented to verify the effectiveness of the proposed control scheme.

Abstract Background Familial dilated cardiomyopathy (DCM) is a genetic cardiomyopathy that is associated with reduced left ventricle function or systolic function. Fifty-one DCM-causative genes have been reported, most of which are inherited in an autosomal dominant manner. However, recessive DCM-causative gene is rarely observed. Methods Whole-exome sequencing (WES) was performed in a consanguineous family with DCM to identify candidate variants. Sanger sequencing was utilized to confirm the variant. We then checked the DCM candidate gene in 210 sporadic DCM cases. We next explored BICD2 function in both embryonic and adult bicd2-knockout zebrafish models. In vivo cardiac function of bicd2-knockout fish was detected by echocardiography and RNA-seq. Results We identified an autosomal recessive and evolutionarily conserved missense variant, NM_001003800.1:c.2429G > A, in BICD2, which segregated with the disease phenotype in a consanguineous family with DCM. Furthermore, we confirmed the presence of BICD2 variants in 3 sporadic cases. Knockout of bicd2 resulted in partial embryonic lethality in homozygotes, suggesting a vital role for bicd2 in embryogenesis. Heart dilation and decreased ejection fraction, cardiac output and stroke volume were observed in bicd2-knockout zebrafish, suggesting a phenotype similar to human DCM. Furthermore, RNA-seq confirmed a larger transcriptome shift in in bicd2 homozygotes than in heterozygotes. Gene set enrichment analysis of bicd2-deficient fish showed the enrichment of altered gene expression in cardiac pathways and mitochondrial energy metabolism. Conclusions Our study first shows that BICD2 is a novel candidate gene associated with familial DCM, and our findings will facilitate further insights into the molecular pathological mechanisms of DCM.

Mesenchymal stem cells (MSCs) are one of the most potent therapeutic strategies for repairing cardiac injury. It has been shown in the latest studies that MSCs cannot survive in the heart for a long time. Consequently, the exosomes secreted by MSCs may dominate the repair of heart injury and promote the restoration of cardiac cells, vascular proliferation, immune regulation, etc. Based on the current research, the progress of the acting mechanism, application prospects and challenges of exosomes, including non-coding RNA, in repairing cardiac injuries are summarised in this article.

Ankyrin repeat and suppression-of-cytokine-signaling box (Asb) proteins, a subset of ubiquitin ligase E3, include Asb5 with six ankyrin-repeat domains. Zebrafish harbor two asb5 gene isoforms, asb5a and asb5b. Currently, the effects of asb5 gene inactivation on zebrafish embryonic development and heart function are unknown. Using CRISPR/Cas9, we generated asb5a-knockout zebrafish, revealing no abnormal phenotypes at 48 h post-fertilization (hpf). In situ hybridization showed similar asb5a and asb5b expression patterns, indicating the functional redundancy of these isoforms. Morpholino interference was used to target asb5b in wild-type and asb5a-knockout zebrafish. Knocking down asb5b in the wild-type had no phenotypic impact, but simultaneous asb5b knockdown in asb5a-knockout homozygotes led to severe pericardial cavity enlargement and atrial dilation. RNA-seq and cluster analyses identified significantly enriched cardiac muscle contraction genes in the double-knockout at 48 hpf. Moreover, semi-automatic heartbeat analysis demonstrated significant changes in various heart function indicators. STRING database/Cytoscape analyses confirmed that 11 cardiac-contraction-related hub genes exhibited disrupted expression, with three modules containing these genes potentially regulating cardiac contractile function through calcium ion channels. This study reveals functional redundancy in asb5a and asb5b, with simultaneous knockout significantly impacting zebrafish early heart development and contraction, providing key insights into asb5’s mechanism.

In order to get accurate position tracking and effective system constraint together for tank gun control systems, a fuzzy system-based barrier adaptive iterative learning control scheme is proposed. Firstly, the error tracking strategy is applied to solve the initial position problem of tank gun iterative learning control systems. Then, a barrier Lyapunov function is adopted to controller design for the system constraint. In addition, a fuzzy system is used as an approximator to compensate for the nonparametric uncertainties, and difference learning learning approach is used to estimate the optimal parameters of fuzzy systems. It is shown that the system constraints are guaranteed and position tracking error converges to a tunable residual set as the iteration number increases.

BackgroundAtrioventricular nodal reentrant tachycardia (AVNRT) is a common arrhythmia. Growing evidence suggests that family aggregation and genetic factors are involved in AVNRT. However, in families with a history of AVNRT, disease-causing genes have not been reported.ObjectiveTo investigate the genetic contribution of familial AVNRT using a whole-exome sequencing (WES) approach.MethodsBlood samples were collected from 20 patients from nine families with a history of AVNRT and 100 control participants, and we systematically analyzed mutation profiles using WES. Gene-based burden analysis, integration of previous sporadic AVNRT data, pedigree-based co-segregation, protein-protein interaction network analysis, single-cell RNA sequencing, and confirmation of animal phenotype were performed.ResultsAmong 95 related reference genes, seven candidate pathogenic genes have been identified both in sporadic and familial AVNRT, including CASQ2, AGXT, ANK2, SYNE2, ZFHX3, GJD3, and SCN4A. Among the 37 reference genes from sporadic AVNRT, five candidate pathogenic genes were identified in patients with both familial and sporadic AVNRT: LAMC1, ryanodine receptor 2 (RYR2), COL4A3, NOS1, and ATP2C2. To identify the common pathogenic mechanisms in all AVNRT cases, five pathogenic genes were identified in patients with both familial and sporadic AVNRT: LAMC1, RYR2, COL4A3, NOS1, and ATP2C2. Considering the unique internal candidate pathogenic gene within pedigrees, three genes, TRDN, CASQ2, and WNK1, were likely to be the pathogenic genes in familial AVNRT. Notably, the core calcium-signaling pathway may be closely associated with the occurrence of AVNRT, including CASQ2, RYR2, TRDN, NOS1, ANK2, and ATP2C2.ConclusionOur pedigree-based studies demonstrate that RYR2 and related calcium signaling pathway play a critical role in the pathogenesis of familial AVNRT using the WES approach.

Seepage in the underground rock and soil is one of the main causes of geological disasters. Precursor information for geological disasters is provided by accurately measuring the seepage flow in rock and soil, so as to provide disaster warnings in time. This article analyzes the principle of seepage measurement in rock and soil based on heat transfer, deduces the relationship between the flow rate and temperature of the fluid with a seepage sensor, designs and manufactures an entire seepage measurement sensor, and designs a seepage measurement circuit. Finally, a set of portable geotechnical seepage measuring instruments is designed. An experimental platform is designed to realize seepage flow and temperature change experiments with the seepage sensor, it is proved that the sensor can effectively measure the seepage flow for different experimental samples, the measurement range is 0.06–0.160 ml/s. Based on the measured characteristic temperature of the seepage sensor, the calculated seepage flow is obtained, the relative error between the calculated value and the measured value is within 3%.

Abstract Background Atrioventricular nodal reentry tachycardia (AVNRT) is the most common manifestation of paroxysmal supraventricular tachycardia (PSVT). Increasing data have indicated familial clustering and participation of genetic factors in AVNRT, and no pathogenic genes related to AVNRT have been reported. Methods Whole‐exome sequencing (WES) was performed in 82 patients with AVNRT and 100 controls. Reference genes, genome‐wide association analysis, gene‐based collapsing, and pathway enrichment analysis were performed. A protein‐protein interaction (PPI) network was then established; WES database in the UK Biobank and one only genetic study of AVNRT in Denmark were used for external data validation. Results Among 95 reference genes, 126 rare variants in 48 genes were identified in the cases (minor allele frequency G, p.Asn1551Ser) in our study was also detected in the Danish study. Considering the gene functional roles and external data validation, the most likely candidate genes were SCN1A, PRKAG2, RYR2, CFTR, NOS1, PIK3CB, GAD2, and HIP1R. Conclusion The preliminary results first revealed potential candidate genes such as SCN1A, PRKAG2, RYR2, CFTR, NOS1, PIK3CB, GAD2, and HIP1R, and the pathways mediated by these genes, including neuronal system/neurotransmitter release cycles or ion channels/cardiac conduction, might be involved in AVNRT.

In this paper, an adaptive iterative learning control scheme is proposed to solve the trajectory-tracking problem for tank gun servo systems with input deadzone and arbitrary initial states. A time-varying boundary layer is constructed to deal with the nonzero initial error during the iterative learning controller design. Neural network control and robust control are jointly used to compensate uncertainties and deadzone nonlinearity. The ideal weight of neural network and the upper bound of noncontinuous uncertainties are estimated by using difference learning method. As the iteration number increases, the filtering error can converge to the time-varying boundary layer. All signal are guaranteed to be bounded. A simulation example is presented to verify the effectiveness of the proposed scheme.

Stem cells possess regenerative powers and multidirectional differentiation potential and play an important role in disease treatment and basic medical research. Urine-derived stem cells (USCs) represent a newly discovered type of stem cell with biological characteristics similar to those of mesenchymal stromal cells (MSCs), including their doubling time and immunophenotype. USCs are noninvasive and can be readily obtained from voided urine and steadily cultured. Based on advances in this field, USCs and their secretions have increasingly emerged as ideal sources. USCs may play regulatory roles in the cellular immune system, oxidative stress, revascularization, apoptosis and autophagy. This review summarizes the applications of USCs in tissue regeneration and various disease treatments. Furthermore, by analysing their limitations, we anticipate the development of more feasible therapeutic strategies to promote USC-based individualized treatment.

Optical devices play an important role in different fields, such as refractive index detection in food processing and the biochemical industry. In our work, a novel nanoscale optical structure, composed of a metal-insulator-metal waveguide with a stub and a horizontal number eight-shape cavity (HNEC), is presented. The transmission properties of this structure are investigated in detail by using finite element method The effects of geometric parameters on sensing performance are studied in detail. Moreover, the influences of an asymmetric resonator caused by shifting central rectangular cavity of HNEC on transmission spectrum are discussed. The changing parameters of HNEC resonator have different effects on different resonance dips. Then, when the parameters of this presented structure are fixed as a of 540 nm, b of 340 nm, S of 0, l of 70 nm and g of 10 nm, this intriguing structure can serve as a refractive index sensor, whose maximum sensitivity can reach 1,500 nm/refractive index unit with a figure of merit of 75. Therefore, this structure will contribute to the development of miniaturization of optical devices.

This paper proposes an adaptive learning control scheme to solve high-precision velocity tracking problem for tank gun control servo systems. Lyapunov approach is used to design the learning controller, with alignment condition used to cope with initial problem of iterative learning control. Robust control technique and adaptive learning control technique are synthesized to handle nonlinear uncertainties and external disturbances. The unknown parameters are estimated according to the full saturation difference learning strategy. As the iteration number increases, the system state can accurately track the reference signal over the whole time interval, and all signal are guaranteed to be bounded.

The detection of methane has always been an important part of coal mine safety. In order to improve the methane measurement accuracy in coal mines and to determine the influence of environmental interference factors on the measurement results, we designed a spherical, experimental chamber simulating the on-site environment of an underground coal mine containing methane, in which various environmental interference factors can be superimposed. The simulation chamber can generate a uniform and controllable dust environment, a controllable methane environment with concentrations below that which would trigger an alarm, controllable humidity, and environments characterized by other interference factors. Based on computational simulations of the experimental chamber with varying dust-particle-concentration distributions using a single particle size, an optimal design for the chamber has been realized in terms of the rapid mixing of dust and the flow field. Finally, we constructed an underground methane concentration measurement system for coal mines and assessed the influences of different dust concentrations and relative humidity values on the performance of methane measurements, providing a means for improving the measurement accuracy of underground coal mine, spectral, absorption-type methane sensors.

Herein, an ultra compact plasmonics-based refractive index nanosensor is designed consisting of a metal–insulator-metal (MIM) waveguide with a silver-bar and a triangle stub, coupled with a half-ring resonator which can excite Fano resonance. The finite element method (FEM) is used to analyze the transmission spectra of the proposed design. The transmission spectra showed that there were typical Fano resonance line shapes, which roots in a coupling between the broadband state of triangle stub and the narrowband sta te of the half-ring. The effects of structural parameters of the whole system on transmission properties were analyzed, respectively. And the maximum sensitivity (S) of the system obtains 1723 nm/RIU, and figure of merit (FOM) can obtain 51. The proposed system has promising applications for integrated circuits, especially in nanophotonic sensors.

Cardiovascular diseases (CVDs), which are associated with high morbidity and mortality worldwide, include atherosclerosis (AS), hypertension, heart failure (HF), atrial fibrillation, and myocardial fibrosis. CVDs are influenced by the diversity, distribution, and metabolites of intestinal microflora, and their risk can be reduced through physical activity (PA) such as regular exercise. PA benefits the metabolic changes that occur in the gut microbiota (GM). The major metabolites of the GM influence pathogenesis of CVDs through various pathways. However, the relationship between PA and GM is less well understood. In this review, we discuss the impacts of different types of PA on intestinal microflora including the diversity, distribution, metabolites, and intestinal barrier function including intestinal permeability, with a focus on the mechanisms by which PA affects GM. We also discuss how GM influences CVDs. Finally, we summarize current research and knowledge on the effects of PA on CVD via regulation of the GM and intestinal function. More understanding of relevant relationship between PA and GM may provide hope for the prevention or treatment of CVDs. Furthermore, a better understanding of regulation of the GM and intestinal function may lead to novel diagnostic and therapeutic strategies, improving the clinical care of CVD patients.

Exercise-induced cardiac remodeling has aroused public concern for some time, as sudden cardiac death is known to occur in athletes; however, little is known about the underlying mechanism of exercise-induced cardiac injury. In the present study, we established an excessive exercise-induced pathologic cardiac hypertrophy model in zebrafish with increased myocardial fibrosis, myofibril disassembly, mitochondrial degradation, upregulated expression of the pathological hypertrophy marker genes in the heart, contractile impairment, and cardiopulmonary function impairment. High-throughput RNA-seq analysis revealed that the differentially expressed genes were enriched in the regulation of autophagy, protein folding, and degradation, myofibril development, angiogenesis, metabolic reprogramming, and insulin and FoxO signaling pathways. FOXO proteins may be the core mediator of the regulatory network needed to promote the pathological response. Further, PPI network analysis showed that pik3c3, gapdh, fbox32, fzr1, ubox5, lmo7a, kctd7, fbxo9, lonrf1l, fbxl4, nhpb2l1b, nhp2, fbl, hsp90aa1.1, snrpd3l, dhx15, mrto4, ruvbl1, hspa8b, and faub are the hub genes that correlate with the pathogenesis of pathological cardiac hypertrophy. The underlying regulatory pathways and cardiac pressure-responsive molecules identified in the present study will provide valuable insights for the supervision and clinical treatment of pathological cardiac hypertrophy induced by excessive exercise.

Master regulator genes (MRGs) have become a hot topic in recent decades. They not only affect the development of tissue and organ systems but also play a role in other signal pathways by regulating additional MRGs. Because a MRG can regulate the concurrent expression of several genes, its mutation often leads to major diseases. Moreover, the occurrence of many tumors and cardiovascular and nervous system diseases are closely related to MRG changes. With the development in omics technology, an increasing amount of investigations will be directed toward MRGs because their regulation involves all aspects of an organism’s development. This review focuses on the definition and classification of MRGs as well as their influence on disease regulation.

A plasmonic refractive index nanosensor structure consisting of a metal-insulator-metal (MIM) waveguide with two symmetrical rectangle baffles coupled with a connected-concentric-double rings resonator (CCDRR) is presented. In this study, its transmission characteristics were investigated using the finite element method (FEM). The consequences, studied via simulation, revealed that the transmission spectrum of the system presents a sharp asymmetric Fano profile due to the destructive interference between the wide-band mode of two rectangle baffles on the bus waveguide and the narrow-band mode of the CCDRR. The effects of the geometric parameters of the structure on the transmission characteristics were investigated comprehensively. A sensitivity of 2260 nm/RIU and figure of merit (FOM) of 56.5 were the best levels of performance that the designed structure could achieve. In addition, the system could act as a sensor for use for temperature sensing, with a sensitivity that could reach 1.48 nm/°C. The designed structure advances with technology with new detection positions and has good application prospects in other high-sensitivity nanosensor fields, for example, acting as a biosensor to detect the hemoglobin level in the blood.

A nanostructure comprising the metal-insulator-metal (MIM) bus waveguide with a stub coupled with a racetrack ring resonator is designed. The spectral characteristics of the proposed structure are analyzed via the finite element method (FEM). The results show that there is a sharp Fano resonance profile and electromagnetically induced transparency (EIT)-like effect, which are excited by a coupling between the MIM bus waveguide with a stub and the racetrack ring resonator. The normalized HZ field is affected by the displacement of the ring from the stub x greatly. The influence of the geometric parameters of the sensor design on the sensing performance is discussed. The sensitivity of the proposed structure can reach 1774 nm/RIU with a figure of merit of 61. The proposed structure has potential in nanophotonic sensing applications.

A novel induction heating coil is proposed and designed as a shrink-fit tool holder. An electromagnetic field analysis of the coil with different winding methods is conducted using the ANSYS finite element analysis software and an appropriate coil structure is determined, based on the simulated electromagnetic field distribution cloud maps. The magnetic field in the X−Y plane is increased by one order of magnitude around the surface with the addition of the designed magnetic slot, as well as improving the magnetic leakage. The electromagnetic field strength in the middle of the coil is greatly increased, up to 2.312 × 104 A/m, by the addition of a designed magnetic ring covering the top of the coil. The distribution of the three-dimensional temperature field is obtained by the ANSYS workbench transient thermal analysis software, based on the selected coil. Hot-loading equipment used for shrink-fit tool holders are implemented with diameter-selection, power, and heating time-setting functions. Experiments on different types of tool holders are carried out to obtain optimal heating parameters and to verify the reliability of the implemented heating equipment. Through experimental testing, the inserting and pulling out temperature is found to be about 270 °C for the BT40-SF06 and about 285 °C for the BT40-SF10. According to the experimental results, the simulated temperature field is in good agreement with the measured result. The optimal heating parameters of the heating equipment are determined, which proves the correctness of the heating method of the shrink-fit tool holder.

The online measurement of ground water quality, as one important area of water resource protection, can provide real-time measured water quality parameters and send out warning information in a timely manner when the water resource is polluted. Based on ultraviolet (UV) spectrophotometry, a remote online measurement method is proposed and used to measure the ground water quality parameters chemical oxygen demand (COD), total organic carbon (TOC), nitrate nitrogen (NO3−N), and turbidity (TURB). The principle of UV spectrophotometry and the data processing method are discussed in detail, the correlated mathematical modeling of COD and TOC is given, and a confirmatory experiment is carried out. Turbidity-compensated mathematical modeling is proposed to improve the COD measurement accuracy and a confirmatory experiment is finished with turbidity that ranges from 0 to 100 NTU (Nephelometric Turbidity Unit). The development of a measurement instrument to detect the ground water COD, TOC, NO3−N, and TURB is accomplished; the test experiments are completed according to the standard specification of China’s technical requirement for water quality online automatic monitoring of UV, and the absolute measuring errors of COD, TOC, and NO3−N are smaller than 5.0%, while that of TURB is smaller than 5.4%, which meets the requirements for the online measurement of ground water quality.

Surface and underground stretched deformation is one of the most important physical measurement quantities for geological-disaster monitoring. In this study, a parallel helical sensing cable (PHSC) based on the time–domain reflectometry (TDR) technique is proposed and used to monitor large ground stretched deformation. First, the PHSC structure and manufacturing process are introduced, and then, distributed capacitance, distributed inductance, and characteristic impedance were derived based on the proposed stretched-structure model. Next, the relationship between characteristic impedance and stretched deformation was found, and the principle of distributed deformation measurement based on the TDR technique and PHSC characteristic impedance was analyzed in detail. The function of the stretched deformation and characteristic impedance was obtained by curve fitting based on the theoretically calculated results. A laboratory calibration test was carried out by the designed tensile test platform. The results of multi-point positioning and the amount of stretched deformation are presented by the tensile test platform, multi-point positioning measurement absolute errors were less than 0.01 m, and the amount of stretched deformation measurement absolute errors were less than 3 mm, respectively. The measured results are in good agreement with the theoretically calculated results, which verify the correctness of theoretical derivation and show that a PHSC is very suitable for the distributed measurement of the ground stretched deformation.

A four-way quadrature signals generator with precise phase modulation is presented. It consists of a phase precision regulator and a frequency divider. The phase precision regulator generates two programmable currents by controlling the conduction of the tail current sources and then changes the currents into two bias voltages which are superimposed on the clock signals to adjust the phase difference of the four quadrature signals generated by the frequency divider, making the phase difference of 90 degrees. The four quadrature signals’ generator with precise phase modulation has been implemented in a 0.18 μm mixed-signal and RF 1P6M CMOS technology. The size of the chip including the pads is 675 μm⁎690 μm. The circuit uses a supply voltage of 1.8 V, a bias current of 7.2 μA, and the bits of phase-setting input level n=6 in the design. The measured results of the four orthogonal signals’ phase error can reach ±0.1°, and the phase modulation range can reach ±3.6°.

Previous studies have demonstrated that Smyd1 plays a critical role in cardiomyocyte differentiation, cardiac morphogenesis and myofibril organization. In this study, we uncovered a novel function of Smyd1 in the regulation of endothelial cells (ECs). Our data showed that Smyd1 is expressed in vascular endothelial cells, and knockdown of SMYD1 in endothelial cells impairs EC migration and tube formation. Furthermore, Co-IP and GST pull-down assays demonstrated that SMYD1 is associated with the Serum Response Factor (SRF). EMSA assays further showed that SMYD1 forms a complex with SRF and enhances SRF DNA binding activity. Our studies indicate that SMYD1 serves as an SRF-interacting protein, enhances SRF DNA binding activity, and is required for EC migration and tube formation to regulate angiogenesis.

Geft is a guanine nucleotide exchange factor, which can specificallyactivate Rho family of small GTPase by catalyzing theexchange of bound GDP for GTP. Geft is highly expressed inthe excitable tissue as heart and skeletal muscle and plays importantroles in many cellular processes, such as cell proliferation,migration, and cell fate decision. However, the invivo role of Geft remains unknown. Here, we generated a Geftconditional knockout mouse by flanking exons 5-17 of Geftwith loxP sites. Cre-mediated deletion of the Geft gene in heartusing Mef2c-Cre transgenic mice resulted in a dramatic decreaseof Geft expression. Geft knockout mice develop normallyand exhibit no discernable phenotype, suggesting Geft isdispensable for the development of the second heart field inmouse. The Geft conditional knockout mouse will be a valuablegenetic tool for uncovering the in vivo roles of Geft duringdevelopment and in adult homeostasis. (BMB reports2012; 45(3): 153-158)

Some studies have reported that angiotensin converting enzyme (ACE) and angiotensinogen (AGT) genes have been associated with hypertrophic cardiomyopathy (HCM). However, there have been inconsonant results among different studies. To clarify the influence of ACE and AGT on HCM, a systemic review and meta-analysis of case-control studies were performed. The following databases were searched to indentify related studies: PubMed database, the Embase database, the Cochrane Central Register of Controlled Trials database, China National Knowledge Information database, and Chinese Scientific and Technological Journal database. Search terms included "hypertrophic cardiomyopathy", "angiotensin converting enzyme" (ACE) or "ACE" and "polymorphism or mutation". For the association of AGT M235T polymorphism and HCM, "angiotensin converting enzyme" or "ACE" was replaced with "angiotensinogen". A total of seventeen studies were included in our review. For the association of ACE I/D polymorphism and HCM, eleven literatures were included in the meta-analysis on association of penetrance and genotype. Similarly, six case-control studies were included in the meta-analysis for AGT M235T. For ACE I/D polymorphism, the comparison of DI/II genotype vs DD genotype was performed in the present meta-analysis. The OR was 0.73 (95% CI: 0.527, 0.998, P = 0.049, power = 94%, alpha = 0.05) after the study which deviated from Hardy-Weinberg Equilibrium was excluded, indicating that the ACE I/D gene polymorphism might be associated with HCM. The AGT M235T polymorphism did not significantly affect the risk of HCM. In addition, ACE I/D gene polymorphism did not significantly influence the interventricular septal thickness in HCM patients. In conclusion, the ACE I/D polymorphism might be associated with the risk of HCM.

Pygo is a nuclear protein containing two conserved domains, NHD and PHD, which play important roles in embryonic development and carcinogenesis. Pygo was first identified as a core component of the Wnt/β-catenin signalling pathway. However, it has also been reported that the function of Pygo is not always Wnt/β-catenin signalling dependent. In this review, we summarise the functions of both domains of Pygo and show that their functions are synergetic. The PHD domain mainly combines with transcription co-factors, including histone 3 and Bcl9/9l. The NHD domain mainly recruits histone methyltransferase/acetyltransferase (HMT/HAT) to modify lysine 4 of the histone 3 tail (H3K4) and interacts with Chip/LIM-domain DNA-binding proteins (ChiLS) to form enhanceosomes to regulate transcriptional activity. Furthermore, we summarised chromatin modification differences of Pygo in Drosophila (dPygo) and vertebrates, and found that Pygo displayes a chromatin silencing function in Drosophila, while in vertebates, Pygo has a chromatin-activating function due to the two substitution of two amino acid residues. Next, we confirmed the relationship between Pygo and Bcl9/9l and found that Pygo--Bcl/9l are specifically partnered both in the nucleus and in the cytoplasm. Finally, we discuss whether transcriptional activity of Pygo is Wnt/β-catenin dependent during embryonic development. Available information indications that the transcriptional activity of Pygo in embryonic development is either Wnt/β-catenin dependent or independent in both tissue- specific and cell-specific-modes. [ABSTRACT FROM AUTHOR]

Multi-objective design is very common in electrical engineering, and the development of new multi-objective optimizers becomes recently a topical issue in computational electromagnetics because of the unavailability of a universal multiobjective optimizer. In this regard, an improved physical programming (PP) method is presented to solve multi-objective electromagnetic inverse problems. The improvements include: (1) the multi-pseudo preference concept is introduced to overcome the deficiency of existing PP method in finding only one Pareto solution in a simulation and enhance the usage rate of sampling points; (2) a novel dynamically guiding mechanism is proposed to improve the computational efficiency and to provide the evolutionary direction; (3) some new rules for algorithm parameter updating are proposed to realize the two ultimate goals of an idea multi-objective optimizer of finding as many as possible Pareto optimal solutions and having them uniformly distributed on the Pareto Front. The results of typical mathematic test functions and a practical optimization design demonstrate the validity and advantages of the proposed method. [ABSTRACT FROM AUTHOR]

Background: Ventricular conduction blocks (VCBs) are associated with poor outcomes in patients with known cardiac diseases. However, the prognostic implications of VCB patterns in dilated cardiomyopathy (DCM) patients need to be evaluated. The purpose of this study was to determine all-cause mortality in patients with DCM and VCB.Methods: This cohort study included 1119 DCM patients with a median follow-up of 34.3 (19.5-60.8) months, patients were then divided into left bundle branch block (LBBB), right bundle branch block (RBBB), intraventricular conduction delays (IVCD) and narrow QRS groups. The all-cause mortality was assessed using Kaplan-Meier survival curves and Cox regression.Results: Of those 1119 patients, the all-cause mortality rates were highest in patients with IVCD (47.8, n = 32), intermediate in those with RBBB (32.9, n = 27) and LBBB (27.1 %, n = 60), and lowest in those with narrow QRS (19.9 %, n = 149). The all-cause mortality risk was significantly different between the VCB and narrow QRS group (log-rank χ2 = 51.564, P < 0.001). The presence of RBBB, IVCD, PASP ≥ 40 mmHg, left atrium diameter and NYHA functional class were independent predictors of all-cause mortality in DCM patients.Conclusions: Our findings indicate that RBBB and IVCD at admission,but not LBBB, were independent predictors of all-cause mortality in patients with DCM. [ABSTRACT FROM AUTHOR]

Background: Previous studies reported that Atorvastatin (ATOR) can improve the efficacy of Mesenchymal stem cells (MSCs) transplantation after acute myocardial infarction (AMI). However, the results of those studies were inconsistent. To clarify the beneficial effects of atorvastatin added to the cell therapy with MSCs in animal model of acute myocardial infarction (AMI), we performed a systematic review and meta-analysis of case-control studies.Methods: Searches were performed using the PubMed database, the Excerpta Medica Database (Embase), the Science Citation Index, the China National Knowledge Information database, the Wanfang database, and the Chinese Scientific and Technological Journal Database (VIP database). The search term included "Atorvastatin (or Ator)", "Mesenchymal Stem Cells (or Mesenchymal Stem Cell or MSC or MSCs)" and "Acute Myocardial Infarction (or Myocardial Infarction or AMI or MI)". The endpoints were the left ventricular ejection fraction (LVEF) in animal model with AMI.Results: In total, 5 studies were included in the meta-analysis. Pooled analysis indicated a significant LVEF difference at 4 weeks follow-up between MSCs + ATOR combine group and MSCs alone group (95 % CI, 9.09-13.62 %; P < 0.01) with heterogeneity (P = 0.28; P >0.05) and inconsistency (I(2): 22 %).Conclusions: Atorvastatin can enhance the existing effects of MSCs transplantation, and this combinational therapy is a superior cell/pharmacological therapeutic approach that merits future preclinical and clinical studies. [ABSTRACT FROM AUTHOR]

An improved vector cross-entropy (CE) method is proposed to provide a potential candidate for solving multiobjective inverse problems with a large number of variables. To balance the exploitation and exploration searches, the whole iterative process is divided into two phases: diversification and intensification phases. Different parameter evolutionary mechanisms of the probability density functions (pdfs) are proposed for different phases. To speed up the convergence rate, a dynamic evolutionary mechanism is proposed. To enhance the diversity of the sampling points, a mutation manipulation is introduced. The ZDT test functions and a high frequency inverse problem are used as the case studies to testify the effectiveness and efficiency of the proposed method. [ABSTRACT FROM AUTHOR]

Background. Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure with high morbidity and mortality. Although more than 40 genes have been reported to cause DCM, the role of genetic testing in clinical practice is not well defined. Mutations in the troponin T (TNNT2) gene represent an important subset of known disease-causing mutations associated with DCM. Therefore, the aim of the present study was to determine the genetic variations in TNNT2 and the associations of those variations with DCM in Chinese patients. Methods. An approximately 4kb fragment of the TNNT2 gene was isolated from 103 DCM patients and 192 healthy controls and was analyzed by DNA sequence analysis for genetic variations. Results. A total of 6 TNNT2mutations were identified in 99 patients, including a G321Tmissensemutation (Leu84Phe) and 5 novel intronicmutations. Alleles of two novel SNPs (c.192 + 353 C>A, OR = 0.095, 95% CI: 0.013-0.714, p= 0.022; c.192 + 463 G>A, OR = 0.090, 95% CI: 0.012-0.675, p = 0.019) and SNP rs3729843 (OR = 1.889, 95%CI: 1.252-2.852; p = 0.002) were significantly correlated with DCM. Conclusions. These results suggest that the missensemutation (Leu84Phe) and two novel SNPs (c.192+353 C>A, c.192+463 G>A) in TNNT2 gene might be associated with DCM in the Chinese population. [ABSTRACT FROM AUTHOR]

Background: Recent studies have demonstrated that myocardial calpain triggers caspase-3 activation and myocardial apoptosis in models of sepsis, whereas the inhibition of calpain activity down-regulates myocardial caspase-3 activation and apoptosis. However, the mechanism underlying this pathological process is unclear. Therefore, in this study, our aim was to explore whether the Hsp90/Akt signaling pathway plays a role in the induction of myocardial calpain activity, caspase-3 activation and apoptosis in the septic mice. Methods: Adult male C57 mice were injected with lipopolysaccharide (LPS, 4 mg/kg, i.p.) to induce sepsis. Next, myocardial caspase-3 activity and the levels of Hsp90/p-Akt (phospho-Akt) proteins were detected, and apoptotic cells were assessed by performing the TUNEL assay. Results: In the septic mice, there was an increase in myocardial calpain and caspase-3 activity in addition to an increase in the number of apoptotic cells; however, there was a time-dependent decrease in myocardial Hsp90/p- Akt protein levels. The administration of calpain inhibitors (calpain inhibitor-? or PD150606) prevented the LPSinduced degradation of myocardial Hsp90/p-Akt protein and its expression in cardiomyocytes in addition to inhibiting myocardial caspase-3 activation and apoptosis. The inhibition of Hsp90 by pretreatment with 17-AAG induced p-Akt degradation, and the inhibition of Akt activity by pretreatment with wortmannin resulted in caspase- 3 activation in wildtype C57 murine heart tissues. Conclusions: Myocardial calpain induces myocardial caspase-3 activation and apoptosis in septic mice via the activation of the Hsp90/Akt pathway. [ABSTRACT FROM AUTHOR]

Background. Idiopathic dilated cardiomyopathy (DCM) is characterized by ventricular chamber enlargement and systolic dysfunction. The pathogenesis of DCM remains uncertain, and the TNNT2 gene is potentially associated with DCM. To assess the role of TNNT2 in DCM, we examined 10 tagging single nucleotide polymorphisms (SNPs) in the patients. Methods. A total of 97 DCM patients and 189 control subjects were included in the study, and all SNPs were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Results. In the TNNT2 gene, there was a significant association between DCM and genotype for the tagging SNPs rs3729547 (X² = 6.63, P = 0.036, OR = 0.650, and 95% CI = 0.453-0.934) and rs3729843 (X² = 9.787, P = 0.008, OR = 1.912, and 95% CI = 1.265-2.890) in the Chinese Han population. Linkage disequilibrium (LD) analysis showed that the SNPs rs7521796, rs2275862, rs3729547, rs10800775, and rs1892028, which are approximately 6kb apart, were in high LD (D′ > 0.80) in the DCM patients. Conclusion. These results suggest that the TNNT2 polymorphisms might play an important role in susceptibility to DCM in the Chinese Han population. [ABSTRACT FROM AUTHOR]

In order to study the impalpable effect of GFP in homozygous heart-specific GFP-positive zebrafish during the early stage, the researchers analyzed the heart function of morphology and physiology at the first 3 days after fertilization. This zebrafish line was produced by a large-scale Tol2 transposon mediated enhancer trap screen that generated a transgenic zebrafish with a heart-specific expression of green fluorescent protein (GFP)-tagged under control of the nppa enhancer. In situ hybridization experiments showed that the nppa:GFP line faithfully recapitulated both the spatial and temporal expressions of the endogenous nppa. Green fluorescence was intensively and specifically expressed in the myocardial cells located both in the heart chambers and in the atrioventricular canal. The embryonic heart of nppa:GFP line developed normally compared with those in the wild type. There was no difference between the nappa:GFP and wild type lines with respect to heart rate, overall size, ejection volume, and fractional shortening. Thus the excess expression of GFP in this transgenic line seemed to exert no detrimental effects on zebrafish hearts during the early stages. [ABSTRACT FROM AUTHOR]

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Abstract  It has been reported that mouse Lbh (limb-bud and heart) can regulate cardiac gene expression by modulating the combinatorial activities of key cardiac transcription factors, as well as their individual functions in cardiogenesis. Here we report the cloning and characterization of the human homolog of mouse Lbh gene, hLBH, from a human embryonic heart cDNA library. The cDNA of hLBH is 2927 bp long, encoding a protein product of 105 amino acids. The protein is highly conserved in evolution across different species from zebra fish, to mouse, to human. Northern blot analysis indicates that a 2.9 kb transcript specific for hLBH is most abundantly expressed in both embryonic and adult heart tissue. In COS-7 cells, hLBH proteins are localized to both the nucleus and the cytoplasm. hLBH is a transcription activator when fused to Gal-4 DNA-binding domain. Deletion analysis indicates that both the N-terminal containing proline-dependent serine/threonine kinase group and the C-terminal containing ERK D-domain motif are required for transcriptional activation. Overexpression of hLBH in COS-7 cells activates the transcriptional activities of activator protein-1 (AP-1) and serum response element (SRE). These results suggest that hLBH proteins may act as a transcriptional activator in mitogen-activated protein kinase signaling pathway to mediate cellular functions. [ABSTRACT FROM AUTHOR]

Abstract  Cardiac differentiation involves a cascade of coordinated gene expression that regulates cell proliferation and matrix protein formation in a defined temporal-spatial manner. Zinc finger-containing transcription factors have been implicated as critical regulators of multiple cardiac-expressed genes, and are thought to be important for human heart development and diseases. Here, we have identified and characterized a novel zinc finger gene named ZNF418 from a human embryo heart cDNA library. The gene spans 13.5 kb on chromosome 19q13.43 encompassing six exons, and transcribes a 3.7-kb mRNA that encodes a protein with 676 amino acid residues. The predicted protein contains a KRAB-A box and 17 tandem C2H2 type zinc finger motifs. Northern blot analysis indicates that ZNF418 is expressed in multiple fetal and adult tissues, but is expressed at higher levels in the heart. Reporter gene assays show that ZNF418 is a transcriptional repressor, and the KRAB motif of ZNF418 represents the basal repressive domain. Overexpression of ZNF418 in COS-7 cells inhibits the transcriptional activity of SRE and AP-1 which may be silenced by siRNA. These results suggest that ZNF418 is a member of the zincfinger transcription factor family and may act as a negative regulator in MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Muscle LIM protein.(MLP) is a cytoskeletal protein located at the 2-disc of sarcomeres. Mutations in the human MLP gene are associated with hypertrophic and dilated cardiomyopathy. MLP has been proposed to be a key player in the stretch-sensing response, but the molecular mechanisms underlying its function in normal and diseased cardiac muscle have not been established. A Drosophila homolog, Mlp84B, displays a similar subcellular localization at the 2-disc of sarcomeres throughout development and in the adult, suggesting Drosophila as a model to study MLP function. Here we employed genetic ablation and cardiac-specific RNA interference (RNAi) knockdown of mlp84B to investigate its role in heart function. We found that Mlp84Bdeficient or heart-specific RNAi knockdown flies exhibit diastolic interval prolongation, heart rhythm abnormalities and a reduced lifespan, while showing no obvious structural phenotype. Our data demonstrate that Mlp84B is essential for normal cardiac function and establish the Drosophila model for the investigation of the mechanisms connecting defective cardiac 2-disc components to the development of cardiomyopathy. [ABSTRACT FROM AUTHOR]

Abstract??The LIM-homeodomain (LIM-HD) proteins have a homeodomain and two N-terminal LIM domains, which consist of a conserved cysteine- and histidine-rich structure of two tandem repeated zinc fingers. LIM domain is involved in protein?protein interactions during transcriptional regulation. LIM-HD proteins are classically suggested as major transcriptional regulators which, in cooperation with other transcription factors, play critical roles in several developing systems and organs, such as nervous system, pancreas, and heart. Here we have cloned the full-length cDNA of humanIsl-2from a human embryo heart cDNA library. The gene contains six exons and spans 5.7?kb in chromosome 15q23 region, and transcribes a 1.9?kb mRNA that encodes a protein with 359 amino acid residues. The predicted protein, containing two tandem LIM motifs in N-terminal and a homeodomain domain, is well conserved, especially in the LIM and DNA-binding domains. Northern blot analysis shows that humanIsl-2is expressed in every human tissue examined at adult stage and during embryonic developmental stages from 34 days to 24 weeks at different levels in tissues. The broad expression ofIsl-2gene in tissues during embryogenesis and adult development suggests that it may be involved in both differentiation and maintenance of these tissues and might play an important role. [ABSTRACT FROM AUTHOR]

G-protein-coupled receptor (GPCR) 48 (Gpr48; Lgr4), a newly discovered member of the glycoprotein hormone receptor subfamily of GPCRs, is an orphan GPCR of unknown function. Using a knockout mouse model, we have characterized the essential roles of Gpr48 in bone formation and remodeling. Deletion of Gpr48 in mice results in a dramatic delay in osteoblast differentiation and mineralization, but not in chondrocyte proliferation and maturation, during embryonic bone formation. Postnatal bone remodeling is also significantly affected in Gpr48-/- mice, including the kinetic indices of bone formation rate, bone mineral density and osteoid formation, whereas the activity and number of osteoclasts are increased as assessed by tartrate-resistant acid phosphatase staining. Examination of the molecular mechanism of Gpr48 action in bone formation revealed that Gpr48 can activate the cAMP-PKA-CREB signaling pathway to regulate the expression level of Atf4 in osteoblasts. Furthermore, we show that Gpr48 significantly downregulates the expression levels of Atf4 target genes/proteins, such as osteocalcin (Ocn; Bglap2), bone sialoprotein (Bsp; Ibsp) and collagen. Together, our data demonstrate that Gpr48 regulates bone formation and remodeling through the cAMP-PKA-Atf4 signaling pathway. [ABSTRACT FROM AUTHOR]