Recent advances of mechanosensitive genes in vascular endothelial cells for the formation and treatment of atherosclerosis

Atherosclerotic cardiovascular disease and its complications are a high-incidence disease worldwide.Numerous studies have shown that blood flow shear has a huge impact on the function of vascular endothelial cells,and it plays an important role in gene regulation of pro-inflammatory,pro-thrombotic,pro-oxidative stress,and cell permeability.Many impor-tant endothelial cell mechanosensitive genes have been discovered,including KLK10,CCN gene family,NRP2,YAP,TAZ,HIF-1α,NF-kB,FOS,JUN,TFEB,KLF2/KLF4,NRF2,and ID1.Some of them have been intensively studied,whereas the relevant regulatory mechanism of other genes remains unclear.Focusing on these mechanosensitive genes will provide new strategies for therapeutic intervention in atherosclerotic vascular disease.Thus,this article reviews the mechanosensitive genes affecting vascular endothelial cells,including classical pathways and some newly screened genes,and summarizes the latest research progress on their roles in the pathogenesis of atherosclerosis to reveal effective therapeutic targets of drugs and provide new insights foranti-atherosclerosis.

Cellular gp96 upregulates AFP expression by blocking NR5A2 SUMOylation and ubiquitination in hepatocellular carcinoma

Alpha-fetoprotein (AFP) is the most widely used biomarker for the diagnosis of hepatocellular carcinoma (HCC). However, asubstantial proportion of HCC patients have either normal or marginally increased AFP levels in serum, and the underlyingmechanisms are not fully understood. In the present study, we provided in vitro and in vivo evidence that heat shock protein gp96promoted AFP expression at the transcriptional level in HCC. NR5A2 was identified as a key transcription factor for the AFP gene, andits stability was enhanced by gp96. A further mechanistic study by co-immunoprecipitation, GST pull-down, and molecular dockingshowed gp96 and the SUMO E3 ligase RanBP2 competitively binding to NR5A2 at the sites spanning from aa 507 to aa 539. Thebinding of gp96 inhibited SUMOylation, ubiquitination, and subsequent degradation of NR5A2. In addition, clinical analysis of HCCpatients indicated that gp96 expression in tumors was positively correlated with serum AFP levels. Therefore, our study uncovered anovel mechanism that gp96 regulates the stability of its client proteins by directly affecting their SUMOylation and ubiquitination.These findings will help in designing more accurate AFP-based HCC diagnosis and progression monitoring approaches.

Anisotropic NdFeB/SmCoCuFeZr composite bonded magnet prepared by warm compaction process

Anisotropic NdFeB/SmCoCuFeZr composite bonded magnets were prepared by warm compaction process. The effects of adding SmCoCuFeZr magnetic powder on the properties of anisotropic bonded NdFeB magnet were investigated in this work. The results show that, both magnetic properties and temperature stability of the bonded magnet can be improved by adding fine SmCoCuFeZr magnetic powder. In the present study, the optimal content of SmCoCuFeZr magnetic powder was about 20 wt.%, in this case, the Br, Hcj, and（BH）maxof the NdFeB/SmCoCuFeZr composite magnet achieved 0.943 T, 1250 kA/m, and168 kJ/m^3, respectively.

Alterations in gut microbiota and physiological factors associated with abdominal aortic aneurysm

Abdominal aortic aneurysm(AAA)is a progressive focal dilatation and weakening of the abdominal aorta,causing 1.3%of all deaths among men aged 65–85 years worldwide.The formation of AAA is a complex process with multiple risk factors.Therefore,this study aimed to determine the relationship of disease severity and physiological factors,and gut microbiota structures in AAA patients.Physiological indicators and fecal 16S rRNA gene sequences from healthy controls and patients with AAA were collected.The correlations between the diameter of the AAA and clinical parameters,and gut microbiota composition were then analyzed separately using multivariable analysis.The diameter of AAA was extremely positively correlated with smoking index,alkaline phosphatase,blood glucose,and blood triglycerides and negatively correlated with prealbumin and Cystatin C.As the diameter of AAA increased,the α-diversity,including Chao 1,Shannon,and Simpson indices,of the gut microbiota decreased and presented a negative linear relationship.Patients with AAA with more severe disease had significantly increased relative abundance of Enterobacteriaceae and decreased relative abundance of Veillonellaceae.A strong correlation was observed between the diameter and physiological data,as well as between diameter and gut microbiota composition.This study could improve the understanding of AAA,and gut microbiota may be a potential target to prevent and treat this deadly disease.