Background: The protein Kruppel-like factor 13 (KLF13) is a member of the KLF family and has been identified as a cardiac transcription factor that is involved in heart development. However, the relationship between KLF13 variants and CHDs in humans remains largely unknown. The present study aimed to screen the KLF13 variants in CHD patients and genetically analyze the functions of these variants. Methods: KLF13 variants were sequenced in a cohort of 309 CHD patients and population-matched healthy controls (n = 200) using targeted sequencing. To investigate the effect of variants on the functional properties of the KLF13 protein, the expression and subcellular localization of the protein, as well as the transcriptional activities of downstream genes and physical interactions with other transcription factors, were assessed.

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Background: The protein Kruppel-like factor 13 (KLF13) is a member of the KLF family that has been identified as a novel cardiac transcription factor which is involved in heart development. However, the relationship between KLF13 variants and CHDs in humans remains largely unknown. The present study aimed to screen the KLF13 variants in CHDs patients and genetically analyze the function of these variants. Methods: KLF13 variants were sequenced in a cohort of 309 CHD patients and population-matched healthy controls (n = 200) using targeted sequencing. To investigate the effect of variants on the functional ability of the KLF13 protein, the expressions and subcellular localization of protein, as well as the transcriptional activities of downstream genes and physically interacted with other transcription factor were assessed. Results: Two novel heterozygous variants, c.487C>T (P163S) and c.467G>A (S156N), were identified in two out of 309 CHDs patients with Tricuspid-valve atresia and transposition of the great arteries, respectively. No variants were found among healthy controls. The variant c.467G>A (S156N) increased protein expression and enhanced functionality compared with that of wild-type, without affecting the subcellular localization. The other variant, c.487C>T (P163S), did not show any abnormalities in protein expression and subcellular localization, however it eliminated the transcriptional activities of downstream target genes and physically interacted with TBX5, another cardiac transcription factor. Conclusion: Our results show that the S156N and P163S variants contributed to CHD etiology. Additionally, our findings suggest that KLF13 may be a potential gene contributing to congenital heart disease.

The purpose of this study is to investigate the cutting performance of amorphous carbon (a-C) coatings and hydrogenated amorphous carbon (a-C:H) coatings on machining 2A50 aluminum alloy. First-principles molecular dynamics simulation was applied to investigate the effect of hydrogen on the interaction between coatings and workpiece. The cross-section topography and internal structure of a-C and a-C:H films were characterized by field emission scanning electron microscopy and Raman spectroscopy. The surface roughness of the deposited films and processed workpiece were measured using a white light interferometer. The results show that the a-C-coated tool had the highest service life of 121 m and the best workpiece surface quality (Sq parameter of 0.23 μm) while the workpiece surface roughness Sq parameter was 0.35 and 0.52 μm when machined by the a-C:H-coated and the uncoated tool, respectively. Meanwhile, the build-up edge was observed on the a-C:H-coated tool and a layer of aluminum alloy was observed to have adhered to the surface of the uncoated tool at its stable stage. An interface model that examined the interactions between H-terminated diamond (111)/Al(111) surfaces revealed that H atoms would move laterally with the action of cutting heat (549 K) and increase the interaction between a-C:H and Al surfaces; therefore, Al was prone to adhere to the a-C:H-coated tool surface. The a-C coating shows better performance on cutting aluminum alloy than the a-C:H coating.