HIV encephalopathy is contributed by macrophages and microglia

Dear Editor,Acquired immunodeficiency syndrome(AIDS),characterized by a significant decrease in the number of CD4^(+)T cells,causes a defective T cell immune response,which subsequently leads to various conditional pathogenic infections and tumors(Calmy et al.,2018;Seligmann et al.,1987).Neurological disorders have been reported in 70%–80%of patients with AIDS(Saylor et al.,2016)。

SIRT6 is an epigenetic repressor of thoracic aortic aneurysms via inhibiting inflammation and senescence

Thoracic aortic aneurysms(TAAs)develop asymptomatically and are characterized by dilatation of the aorta.This is considered a life-threating vascular disease due to the risk of aortic rupture and without effective treatments.The current understanding of the pathogenesis of TAA is still limited,especially for sporadic TAAs without known genetic mutation.Sirtuin 6(SIRT6)expression was significantly decreased in the tunica media of sporadic human TAA tissues.Genetic knockout of Sirt6 in mouse vascular smooth muscle cells accelerated TAA formation and rupture,reduced survival,and increased vascular inflammation and senescence after angiotensin II infusion.Transcriptome analysis identified interleukin(IL)-1βas a pivotal target of SIRT6,and increased IL-1βlevels correlated with vascular inflammation and senescence in human and mouse TAA samples.Chromatin immunoprecipitation revealed that SIRT6 bound to the Il1b promoter to repress expression partly by reducing the H3K9 and H3K56 acetylation.Genetic knockout of Il1b or pharmacological inhibition of IL-1βsignaling with the receptor antagonist anakinra rescued Sirt6 deficiency mediated aggravation of vascular inflammation,senescence,TAA formation and survival in mice.The findings reveal that SIRT6 protects against TAA by epigenetically inhibiting vascular inflammation and senescence,providing insight into potential epigenetic strategies for TAA treatment.

Differential transcriptomic landscapes of multiple organs from SARS-CoV-2 early infected rhesus macaques

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries,how-ever,the underlying mechanism,in particular immune responses in different organs,remains elusive.In this study,comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed.Compared to normal controls,SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs,with drastic transcriptomic changes in cerebral cortex and right ventricle.Intriguingly,cerebral cortex exhibited a hyperinflammatory state evidenced by sig-nificant upregulation of inflammation response-related genes.Meanwhile,expressions of coagulation,angio-genesis and fibrosis factors were also up-regulated in cerebral cortex.Based on our findings,neuropilin 1(NRP1),a receptor of SARS-CoV-2,was significantly elevated in cerebral cortex post infection,accompanied by active immune response releasing inflammatory factors and signal transmission among tissues,which enhanced infection of the central nervous system(CNS)in a positive feedback way,leading to viral encephalitis.Overall,our study depicts a multi-tissue/organ tran-scriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2,and provides important insights into the mechanistic basis for COVID-19-asso-ciated clinical complications.

Genome-wide 5-Hydroxymethylcytosine Profiling Analysis Identifies MAP7D1 as A Novel Regulator of Lymph Node Metastasis in Breast Cancer

Although DNA 5-hydroxymethylcytosine(5 hmC)is recognized as an important epigenetic mark in cancer,its precise role in lymph node metastasis remains elusive.In this study,we investigated how 5 hmC associates with lymph node metastasis in breast cancer.Accompanying with high expression of TET1 and TET2 proteins,large numbers of genes in the metastasis-positive primary tumors exhibit higher 5 hmC levels than those in the metastasis-negative primary tumors.In contrast,the TET protein expression and DNA 5 hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors.Through genomewide analysis of 8 sets of primary tumors,we identified 100 high-confidence metastasis-associated5 hmC signatures,and it is found that increased levels of DNA 5 hmC and gene expression of MAP7 D1 associate with high risk of lymph node metastasis.Furthermore,we demonstrate that MAP7 D1,regulated by TET1,promotes tumor growth and metastasis.In conclusion,the dynamic5 hmC profiles during lymph node metastasis suggest a link between DNA 5 hmC and lymph node metastasis.Meanwhile,the role of MAP7 D1 in breast cancer progression suggests that the metastasis-associated 5 hmC signatures are potential biomarkers to predict the risk for lymph node metastasis,which may serve as diagnostic and therapeutic targets for metastatic breast cancer.