Endocardial cushions, derived from the atrioventricular canal (AVC) and outflow tract (OFT), serve as the primordia for the formation of the septum and valves. Improper morphogenesis of the endocardial cushion leads to septal and valvular abnormalities, which contribute to the largest proportion of congenital heart diseases (CHDs). The development and maturation of the endocardial cushion rely on endothelial-to-mesenchymal transition (EndMT), a process by which endocardial cells undergo morphological remodeling and develop into the endocardial cushion mesenchyme. This biological event is strictly governed by regional signals originating from the myocardium, endocardium, and mesenchyme. Various signaling pathways, including TGFβ/BMP, Wnt, Notch, Hippo/YAP, PI3K/AKT, VEGF, and mechanical stress, are involved in the modulation of endocardial cell proliferation, migration, and mesenchymal transition. Transcription factors, such as SMAD, SNAIL, TWIST, TBX2, SOX9, KLF2/4, and NFATc1, exert distinct effects on endocardial EndMT. Maternal environmental exposures can disrupt signaling pathways and transcriptional network during endocardial cushion development, thereby enhancing susceptibility to CHDs. This review summarizes the mechanistic pathways and transcriptional regulation in AVC endocardial cushion development and EndMT, highlighting their association with CHDs.

目的:评价小分子化合物雷帕霉素、羟氯喹和MC1568对心肌分化效率和心肌分化转录因子Mef2c表达的影响.方法:利用DMSO诱导P19CL6小鼠畸胎瘤干细胞分化为自发跳动的心肌细胞,检测自噬诱导剂雷帕霉素对小鼠P19CL6畸胎瘤细胞向心肌分化的影响,研究相关机制.结果:自噬诱导剂雷帕霉素能够有效促进心肌分化,增强心肌标志性基因表达;自噬抑制剂羟氯喹能抑制DMSO诱导的P19CL6细胞心肌分化.雷帕霉素促进心肌分化转录因子Mef2c表达;采用Mef2c的小分子抑制剂MC1568,则能抑制雷帕霉素诱导的心肌早期和晚期分化标志基因表达.结论:雷帕霉素诱导的Mef2c表达是增强心肌分化能力所必需的.

目的 雷帕霉素是小分子mTOR抑制剂,可激活细胞自噬.本研究检测了雷帕霉素对胚胎干细胞(ES细胞)向心肌分化的影响.方法 采用拟胚体(embryoid body,EB)加抗坏血酸诱导ES细胞向心肌分化.悬浮诱导阶段添加自噬激动剂雷帕霉素或抑制剂羟氯喹,通过免疫印迹检测LC3蛋白剪切以监测细胞自噬水平,通过检测EB球的心肌搏动百分比以及心肌分化标志物troponin-T和α-actinin的表达来评估细胞分化效率.采用real-time PCR检测心肌分化转录因子Mef2c和Isl1 mRNA表达,免疫印迹法检测Oct4表达,进一步阐释雷帕霉素的效应机制.结果 雷帕霉素能够诱导自噬,促进LC3剪切,促进EB球产生自发搏动,增强心肌分化标志基因表达.机制研究发现,雷帕霉素促进心肌转录因子Mef2c和Isl1 mRNA的表达和Oct4在分化细胞的下调.而自噬抑制剂羟氯喹能拮抗雷帕霉素的上述效应.结论 雷帕霉素诱导自噬可以促进心肌转录因子表达和促进干性因子Oct4水平下调,从而促进心肌分化.

4-phenylbutyrate (4-PBA), a terminal aromatic substituted fatty acid, is used widely to specifically attenuate endoplasmic reticulum (ER) stress and inhibit histone deacetylases (HDACs). In this study, we investigated the effect of 4-PBA on cardiac differentiation of mouse embryonic stem (ES) cells. Herein, we found that 4-PBA regulated cardiac differentiation in a stage-specific manner just like trichostatin A (TSA), a well-known HDAC inhibitor. 4-PBA and TSA favored the early-stage differentiation, but inhibited the late-stage cardiac differentiation via acetylation. Mechanistic studies suggested that HDACs exhibited a temporal expression profiling during cardiomyogenesis. Hdac1 expression underwent a decrease at the early stage, while was upregulated at the late stage of cardiac induction. During the early stage of cardiac differentiation, acetylation favored the induction of Isl1 and Nkx2.5, two transcription factors of cardiac progenitors. During the late stage, histone acetylation induced by 4-PBA or TSA interrupted the gene silence of Oct4, a key determinant of self-renewal and pluripotency. Thereby, 4-PBA and TSA at the late stage hindered the exit from pluripotency, and attenuated the expression of cardiac-specific contractile proteins. Overexpression of HDAC1 and p300 exerted different effects at the distinct stages of cardiac induction. Collectively, our study shows that timely manipulation of HDACs exhibits distinct effects on cardiac differentiation. And the context-dependent effects of HDAC inhibitors depend on cell differentiation states marked by the temporal expression of pluripotency-associated genes.

The HaiYang-2B(HY-2B) satellite was successfully launched in October 2018. A multichannel scanning microwave radiometer (SMR) was carried for measuring sea surface temperature(SST), sea surface wind speed (SSW), total water vapor (TWV) and cloud liquid water (CLW) content. In this paper, the initial performance of SMR is evaluated with one month's measured data. The comparisons between the brightness temperature of SMR and that of model and GMI indicate that the measurements of SMR are in good agreement with the results of model and GMI at low frequency. Besides, the contrast between SMR and SSMIS at Sahara Desert and Antarctic ice sheet, and the analysis for the measurements of cold and heat source infer that the measurements at high frequency is valid and accurate. In order to assess the measurements of SMR globally, all the four parameters are retrieved with in-situ statistical regression algorithm and validated with the WindSat gridded products. The RMSE of SST, SSW, TWV, CLW is 0.80 °C, 0.7mmss, 0.86mm and 0.03mm, respectively, which are far better than the required accuracy. In future, with the accumulation of data acquired from SMR, the new precise correction for data and the comparison to the in-situ Argo, buoy and sonde measurements will be made. It is expectable that the accuracy will be further improved.

Correlation radiometer is the basic unit of interferometer or full polarization radiometer which can obtain the correlation of two receiving channels. The paper presents a novel receiving configuration of correlation radiometer using the digital signal processing to fulfill the IQ demodulation and acquire the band of application requirement exactly. This new receiving configuration can eliminate the quadrature errors which can simplify the calibration procedure and acquire exact receiving band which can improve the consistence of multiple parallel receiving channels. This novel receiving configuration which has been applied in L\X-band Full Polarization Aperture Synthesis Microwave Radiometer (FPASMR) establishes the basis of spaceborne engineering application in the future.

Islet 1 (ISL1), a marker of second heart field progenitors, plays a crucial role in cardiomyocyte differentiation and proliferation. However, little is known about transcriptional regulating mechanisms on Isl1 gene expression. Recent studies have demonstrated that Wnt/β-catenin signaling regulates Isl1 expression during heart development. However, the detailed mechanisms still remain unclear. In the present study performed during differentiation of P19CL6 into cardiomyocytes, we explored the underlying regulating mechanisms on Wnt/β-catenin-mediated Isl1 expression after we first confirmed that Wnt/β-catenin signaling promoted cardiomyocyte differentiation partly through Isl1 activation. We found a novel TCF/LEF1 binding site that was located 2300 bp upstream of the Isl1 ATG. Furthermore, Wnt/β-catenin signaling upregulated histone H3K9 acetylation on TCF/LEF1 binding sites on the Isl1 promoter, resulting in upregulation of Isl1 expression. This Wnt-mediated H3K9 acetylation on the Isl1 promoter was modulated by the acetyltransferase CREB-binding protein (CBP), instead of p300, through interaction with β-catenin. Collectively, these results suggest that in early stages of cardiomyocyte differentiation Wnt/β-catenin signaling promotes Isl1 expression via two ways: a novel TCF/LEF1 binding site and H3K9 acetylation conducted by CBP on the Isl1 promoter. To our knowledge, this is the first study reporting Wnt/β-catenin-regulated H3K9 acetylation on promoters of its target genes. And this study gives new insights into transcriptional regulating mechanisms of Wnt-mediated Isl1 expression during cardiomyocyte differentiation.

In this paper, an H∞ state feedback control problem for a generalized state-space system is considered. For the system, we propose a controller module consists of a local controller and a remote one under networked framework. The remote controller could improve the control efficiency of the local controller to the plant when the correlated networked feedback system is working with measurement data lose or transmission delay. We utilize a modified finite sum inequality approach to derive a set of delay-dependent LMI-based sufficient conditions for the admissibility (generalized stability) analysis and controllers synthesis problems, respectively. At the end of this paper, we also present a numerical example to show the feasibility of the proposed conditions.

L\X-band Full Polarization Aperture Synthesis Microwave Radiometer (FPASMR) is a 2-D aperture synthesis radiometer working at L and X-band with full polarization measurement for obtaining high precise measurement of sea salinity and soil moisture. FPASMR consists of dual Y-shaped arrays containing 23 L-band antennas per arm plus one in the center in L-band array and the same numbers of X-band antennas in X-band array. Some early demonstration results of antenna, optical module and calibration are also present.

The Conical Scan Microwave radiometer (CSMR) of the HY-2 satellite is a rotating microwave imager. It covers frequency band from 6.6GHz to 37GHz, which receives the earth radiation by two feed horns, and provides the capability of observing the sea surface temperature, the wind speed, the water vapour and the liquid water etc. It was launched at 16 august 2010. This paper provides an overview of the the instrument's characteristic and the inter-satellite calibration results are also presented.

MIRAS(Microwave Imaging Radiometer by Aperture Synthesis),the only payload of SMOS(Soil Moister and Ocean Salinity),which is a 2-D aperture synthesis radiometer has 72 receivers and about 5000 digital correlation units and it is the most complex radiometer in orbit.The calibration of the MIRAS which is focused on different errors causing by different reasons uses the method step by step.Firstly,the paper introduces the composition of the calibration system.Secondly,the paper introduces the system calibration method.Finally,the process of the calibration is introduced.

A microfluidic device is developed to transport microbubbles (MBs) along a desired trajectory in fluid by introducing the phase-shift to a planar standing surface acoustic wave (SSAW). The radiation force of SSAW due to the acoustic pressure gradient modulated by a phase-shift can move MBs to anticipated potential wells in a programmable manner. The resolution of the transportation is approximately 2.2 µm and the estimated radiation force on the MBs is on the order of 10−9 N. This device can be used for manipulation of bioparticles, cell sorting, tissue engineering, and other biomedical applications.

Programmable microfluidic systems for bioparticles manipulation that could enable automated biological analysis and diagnostics have the potential to revolutionize a wide range of applications in life sciences research, clinical diagnostics, and drug discovery. Several methods such as those based on hydrodynamic force, magnetic tweezers, and dielectrophoresis can manipulate the movement of the bioparticles successfully. However, these methods must be constructed the flow structure, magnetic wire, and electrode in the microchannel respectively, which not only limits the flexibility of manipulation but also makes the sample more likely to be contaminated. In this paper, a programmable microfluidic device is developed to manipulate the microbubbles along an arbitrary trajectory in the microchannel without any structure by introducing phase-shifts to a planar standing surface acoustic wave field. The microbubbles can be transported in a square trajectory, circular trajectory and even helix trajectory via adjusting the relative phase between the excitation signals controlled by LabVIEW program. The results reveal that the microbubbles can be transported over a predetermined distance continuously until they reach the targeted locations. This acoustic programmable microfluidic device would have potential applications on drug screening, cell studies, and other biomedical applications.

Islet 1 (ISL1), a marker of cardiac progenitors, plays a crucial role in cardiogenesis. However, the precise mechanism underlying the activation of its expression is not fully understood. Using the cardiac differentiation model of P19CL6 cells, we show that POU homeodomain protein, OCT1, modulates Isl1 expression in the process of cardiac differentiation. Oct1 knock-down resulted in reduction of Isl1 expression and downregulated mesodermal, cardiac-specific, and signal pathway gene expression. Additionally, the octamer motif located in the proximal region of Isl1 promoter is essential to Isl1 transcriptional activation. Mutation of this motif remarkably decreased Isl1 transcription. Although both OCT1 and OCT4 bound to this motif, it was OCT1 rather than OCT4 that modulated Isl1 expression. Furthermore, the correlation of OCT1 in regulation of Isl1 was revealed by in situ hybridization in early embryos. Collectively, our data highlight a novel role of OCT1 in the regulation of Isl1 expression.

Elastography is an emerging ultrasonic imaging technique; it has a broad clinical application for tissue parameter estimation. We designed a real-time system to measure tissue stiffness information non-invasively based on transient elastography. The system performance mainly depends on the circuit design before the Analog-to-Digital Converter (A/D), especially the preamplifier part which is very sensitive to the noise. How to improve the signal-to-noise (SNR) is the key factor for the system design. In this paper, the Time Gain Control (TGC) design is discussed as an example of the circuit design. Displacement tracking algorithm based on correlation techniques and differentiation are applied to Radio frequency (RF) signals from tissues mimicking phantom and in vivo experiments; the young's modulus of the tissue is estimated from the strain images. The influences of the SNR to the strain image quality are discussed. At the end, an improvement based on the AD9272 is proposed.

Small-animal imaging technology has been rapidly developed for longitudinal screening of laboratory animals raised with disease developments or genetic manipulations. Micro-CT is a noninvasive imaging modality used to assess morphology and function in small-animal imaging. Geometric calibration involves the estimation of a set of parameters that describes the geometry of such systems, and is essential for accurate image reconstruction. Noo F et al (2000) have proposed a new analytic method for calibration of x-ray cone-beam scanners that use a circular path for the cone vertex. In this paper, we use this analytic calibration method for the estimation of the geometric parameters of a practical small-animal imaging micro-CT system. We improve calibration phantom of this method in order to make it more suitable for micro-CT system. The overall performance of the micro-CT system is demonstrated in some results of small-animal imaging. The projection images demonstrated that the adopt method is robust and easy to implement with high precision.

An X-ray computed tomography (CT) simulator based on Geant4 toolkit was developed for simulation of both fan- and cone-beam CT scanners. There major components X-ray tube, phantom and detector are simulated. Different to analytical simulation, this simulation is accordance with imaging physics by adopting the Geant4 toolkit. Compared with ordinary statistical simulation, acceleration investigation and parameters optimization are considered. Also,experiments on beam-hardening and scatter are simulated. As expected, this simulator is not only a tool for acquiring scanning data, but also a tool for evaluating dose, the effect of physical, geometrical and potential artifacts and corresponding correction schemes in CT system.

Three-dimensional medical image visualization becomes an essential part for medical field, including computer-aided diagnosis, surgery planning and simulation, artificial limb surgery, radiotherapy planning, and teaching etc. In this paper, marching cubes algorithm is adopted to reconstruct the 3-D images for the CT image sequence in DICOM format under the VC++6.0 and the visual package VTK platform. The relatively simple interactive operations such as rotation and transfer can be realized on the platform. Moreover, the normal vector and interior point are calculated to form the virtual clipping plane, which is then used to incise the 3-D object. Information of the virtual slice can be obtained, in the mean while the virtual slice images are displayed on the screen. The technique can realize the real time interaction extraction of virtual slice on 3-D CT image. The cuboids structured can be zoomed, moved and circumrotated by operating mouse to incise the 3-D reconstruction object. Real time interaction can be realized by clipping the reconstruction object. The coordinates can be acquired by the mouse clicking in the 3D space, to realize the point mouse pick-up as well angle and distance interactive measurement. We can get quantitative information about 3-D images through measurement.

A high performance micro-tomography (micro-CT) system for insect or small animal imaging has been developed. The system consists of an x-ray source with small focus spot and high brightness, a high precision rotation stage with an object chuck to achieve a cone-beam mode scan, and an x-ray imaging detector. The core of the system is a cooled x-ray imaging detector with high spatial resolution, high sensitivity and ultra-low noise. Since imaging performance of the detector is mostly responsible for the resultant image quality and eventually determines the quality of a tomogram, we have evaluated the imaging characteristics of the detector in terms of modulation-transfer function (MTF), noise-power spectrum (NPS) and give some high quality x-ray digital radiation (DR) and 3D rendered CT images of some insects and a small fish.

The cardiac transcription factor NKX2.5 plays a crucial role in cardiomyogenesis, but its mechanism of regulation is still unclear. Recently, epigenetic regulation has become increasingly recognized as important in differentiation and development. In this study, we used P19CL6 cells to investigate the regulation of Nkx2.5 expression by methylation and acetylation during cardiomyocyte differentiation. During the early stage of differentiation, Nkx2.5 expression was upregulated, but the methylation status of the Nkx2.5 promoter did not undergo significant change; while the acetylation levels of histones H3 and H4 were increased, accompanied by a significant reduction in Hdac1 expression. Suppression of Hdac1 activity stimulated cardiac differentiation accompanied by increased expression of cardiac-specific genes and cell cycle arrest. Overexpression of Hdac1 inhibited cardiomyocyte formation and downregulated the expressions of Gata4 and Nkx2.5. Mimicking induction of the WNT pathway inhibited Hdac1 expression with upregulated Nkx2.5 expression. WNT3a and WNT3 downregulated the expression of Hdac1, contrary to the effect of SFRP2 and GSK3β. Cotransfection of β-catenin and Lef1 significantly downregulated the expression of Hdac1. Our data suggest that WNT signaling pathway plays important roles in the regulation of Hdac1 during the early stage of cardiomyocyte differentiation and that the downregulation of Hdac1 promotes cardiac differentiation.