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Abstract Background Development of hematopoietic stem and progenitor cells (HSPC) is a multi-staged complex process that conserved between zebrafish and mammals. Understanding the mechanism underlying HSPC development is a holy grail of hematopoietic biology, which is helpful for HSPC clinical application. Chromatin conformation plays important roles in transcriptional regulation and cell fate decision; however, its dynamic and role in HSPC development is poorly investigated. Methods We performed chromatin structure and multi-omics dissection across different stages of HSPC developmental trajectory in zebrafish for the first time, including Hi-C, RNA-seq, ATAC-seq, H3K4me3 and H3K27ac ChIP-seq. Results The chromatin organization of zebrafish HSPC resemble mammalian cells with similar hierarchical structure. We revealed the multi-scale reorganization of chromatin structure and its influence on transcriptional regulation and transition of cell fate during HSPC development. Nascent HSPC is featured by loose conformation with obscure structure at all layers. Notably, PU.1 was identified as a potential factor mediating formation of promoter-involved loops and regulating gene expression of HSPC. Conclusions Our results provided a global view of chromatin structure dynamics associated with development of zebrafish HSPC and discovered key transcription factors involved in HSPC chromatin interactions, which will provide new insights into the epigenetic regulatory mechanisms underlying vertebrate HSPC fate decision.

Abstract Background The fusiform aneurysm is a nonsaccular dilatation affecting the entire vessel wall over a short distance. Although PDGFRB somatic variants have been identified in fusiform intracranial aneurysms, the molecular and cellular mechanisms driving fusiform intracranial aneurysms due to PDGFRB somatic variants remain poorly understood. Methods In this study, single-cell sequencing and immunofluorescence were employed to investigate the phenotypic changes in smooth muscle cells within fusiform intracranial aneurysms. Whole-exome sequencing revealed the presence of PDGFRB gene mutations in fusiform intracranial aneurysms. Subsequent immunoprecipitation experiments further explored the functional alterations of these mutated PDGFRB proteins. For the common c.1684 mutation site of PDGFRβ, we established mutant smooth muscle cell lines and zebrafish models. These models allowed us to simulate the effects of PDGFRB mutations. We explored the major downstream cellular pathways affected by PDGFRBY562D mutations and evaluated the potential therapeutic effects of Ruxolitinib. Results Single-cell sequencing of two fusiform intracranial aneurysms sample revealed downregulated smooth muscle cell markers and overexpression of inflammation-related markers in vascular smooth muscle cells, which was validated by immunofluorescence staining, indicating smooth muscle cell phenotype modulation is involved in fusiform aneurysm. Whole-exome sequencing was performed on seven intracranial aneurysms (six fusiform and one saccular) and PDGFRB somatic mutations were detected in four fusiform aneurysms. Laser microdissection and Sanger sequencing results indicated that the PDGFRB mutations were present in smooth muscle layer. For the c.1684 (chr5: 149505131) site mutation reported many times, further cell experiments showed that PDGFRBY562D mutations promoted inflammatory-related vascular smooth muscle cell phenotype and JAK-STAT pathway played a crucial role in the process. Notably, transfection of PDGFRBY562D in zebrafish embryos resulted in cerebral vascular anomalies. Ruxolitinib, the JAK inhibitor, could reversed the smooth muscle cells phenotype modulation in vitro and inhibit the vascular anomalies in zebrafish induced by PDGFRB mutation. Conclusion Our findings suggested that PDGFRB somatic variants played a role in regulating smooth muscle cells phenotype modulation in fusiform aneurysms and offered a potential therapeutic option for fusiform aneurysms.

A double flush-mounted probe method is proposed to analyze the characteristics of intermediate-pressure plasmas (10–100 Pa) by a sheath criterion. The analytical model mainly focuses on the effect of the ion drift velocity in the sheath edge and then provides a correction factor for the measured ion-collection current. The reduction of the ion current is attributed to ion–neutral collisions leading to the modified Bohm velocity. To validate this method, the ion density is calculated and compared with that measured by two types of cylindrical probes, and the results agree well with the data measured by other probes. On the basis of this work, the double flush-mounted probe can be adopted to diagnose plasma parameters accurately, without a reference electrode, in collisional and certain complex plasma environments, such as the reentry plasma sheath.

In this work, an experimental design for generation of the controllable electron density gradient is achieved through a large area oxide coated cathode and two stainless meshes. The large area oxide coated cathode is adopted to produce a large area, uniform and high density plasma, and these two metal meshes are specially designed to control the density and potential of the plasma. A boundary layer with independent electron density gradient and uniform plasma potential is subsequently generated. The controllable electron density gradient can be achieved, and the accompanied electric field can be compensated simultaneously using this design, which could be potentially extended to study the excitation of the plasma instabilities when the strong plasma density gradient exists.

Electrocardiogram (ECG) signal is one of the noninvasive physiological measurement techniques commonly used in cardiac diagnosis. However, in real scenarios, the ECG signal is susceptible to various noise erosion, which affects the subsequent pathological analysis. Therefore, the effective removal of the noise from ECG signals has become a top priority in cardiac diagnostic research. Aiming at the problem of incomplete signal shape retention and low signal-to-noise ratio (SNR) after denoising, a novel ECG denoising network, named attention-based residual dense shrinkage network (ARDSN), is proposed in this paper. Firstly, the shallow ECG characteristics are extracted by a shallow feature extraction network (SFEN). Then, the residual dense shrinkage attention block (RDSAB) is used for adaptive noise suppression. Finally, feature fusion representation (FFR) is performed on the hierarchical features extracted by a series of RDSABs to reconstruct the de-noised ECG signal. Experiments on the MIT-BIH arrhythmia database and MIT-BIH noise stress test database indicate that the proposed scheme can effectively resist the interference of different sources of noise on the ECG signal. [ABSTRACT FROM AUTHOR]

Focuses on the use of a rectangular cross-section discharge tube for the design and fabrication of a helium-neon laser. Design principle; Instrument operation; Output power of the laser; Gain coefficient of the laser medium; Transverse intensity distribution and the beam pattern.