Molecular Genetic Study on HAND2 Gene Promoter in Ventricular Septal Defect.

Ventricular septal defect (VSD), the most common type of congenital heart disease (CHD), is primarily caused by cardiac dysplasia. Heart and neural crest derivatives expressed 2 (HAND2) participates in developing the right heart. The loss of HAND2 expression in humans is closely connected with ventricular septal defects. We used a case-control study to analyze the genetic variations in the HAND2 promoter region in VSD patients and controls. Some statistical analysis methods were used to analyze the association of single nucleotide polymorphisms (SNPs) with VSD. The dual-luciferase reporter assay and electrophoretic mobility shift assay (EMSA) were used to conduct functional analysis and molecular mechanism study of genetic variations. Through sequencing, we identified nine genetic variants in patients with VSD. The SNP rs2276940 G>T and rs2276941 G>A were associated with an increased risk of VSD. The dual-luciferase reporter assay showed that SNP rs2276940 G>T and rs138531627 C>G decreased the transcriptional activity of the HAND2 promoter. Transcription factors (TFs) predicting suggested that all three SNPs may change the binding of TFs. The result of EMSA showed that rs138531627 C>G may create a new binding site for TFs while rs2276940 G>T enhanced the binding affinity for TFs. These results indicated that genetic variants of the HAND2 promoter may increase the risk of VSD, and the molecular mechanism may be the change of the binding affinity of TFs.

Passive Beamforming Design of IRS-Assisted MIMO Systems Based on Deep Learning.

In the intelligent reflecting surface (IRS)-assisted MIMO systems, optimizing the passive beamforming of the IRS to maximize spectral efficiency is crucial. However, due to the unit-modulus constraint of the IRS, the design of an optimal passive beamforming solution becomes a challenging task. The feature input of existing schemes often neglects to exploit channel state information (CSI), and all input data are treated equally in the network, which cannot effectively pay attention to the key information and features in the input. Also, these schemes usually have high complexity and computational cost. To address these issues, an effective three-channel data input structure is utilized, and an attention mechanism-assisted unsupervised learning scheme is proposed on this basis, which can better exploit CSI. It can also better exploit CSI by increasing the weight of key information in the input data to enhance the expression and generalization ability of the network. The simulation results show that compared with the existing schemes, the proposed scheme can effectively improve the spectrum efficiency, reduce the computational complexity, and converge quickly.

[Association of ventricular septal defect with rare variations of the HAND2 gene]. / 室间隔缺损与HAND2åŸºå› ç½•è§å˜å¼‚çš„å ³è”åˆ†æž.

OBJECTIVES: To study the association of ventricular septal defect (VSD) with rare variations in the promoter region of HAND2 gene, as well as related molecular mechanisms. METHODS: Blood samples were collected from 349 children with VSD and 345 healthy controls. The target fragments were amplified by polymerase chain reaction and sequenced to identify the rare variation sites in the promoter region of the HAND2 gene. Dual-luciferase reporter assay was used to perform a functional analysis of the variation sites. Electrophoretic mobility shift assay (EMSA) was used to investigate related molecular mechanisms. TRANSFAC and JASPAR databases were used to predict transcription factors. RESULTS: Sequencing revealed that three variation sites (g.173530852A>G, g.173531173A>G, and g.173531213C>G) were only observed in the promoter region of the HAND2 gene in 10 children with VSD, among whom 4 children had only one variation site. The dual-luciferase reporter assay revealed that g.173531213C>G reduced the transcriptional activity of the HAND2 gene promoter. EMSA and transcription factor prediction revealed that g.173531213C>G created a binding site for transcription factor. CONCLUSIONS: The rare variation, g.173531213C>G, in the promoter region of the HAND2 gene participates in the development and progression of VSD possibly by affecting the binding of transcription factors.