Monocyte activation and cardiovascular disease in HIV infection

Antiretroviral therapy(ART)has increased the lifespan of HIVinfected individuals,which is now approaching that of the general population.However,cardiovascular disease(CVD),including myocardial infarction,stroke,heart failure,and arrhythmia,is still a main cause of mortality in HIVpositive population.The risk of CVD in people living with HIV is about 1.5–2-fold higher than that in the general population.1 Even in those successfully treated with ART,the incidence of CVD is still higher than that in uninfected individuals.2 Thus,in addition to the traditional risk factors associated with CVD,other factors(such as ART per se,inflammation,and immune activation caused by HIV infection)may be involved in CVD development.

Systematic co-delivery of dual agonists to enhance cancer immunotherapy

In the tumor immunosuppressive microenvironment(TIME),antigen presenting cells(APCs)usually exhibit a tumor suppressor phenotype.Toll-like receptors(TLRs)agonists could reprogram M2-type macrophages to M1-type and stimulate dendritic cells(DCs)maturation.The combination of TLR7/8 and TLR9 agonists seems to have synergistic therapeutic efficacy.Here,we designed a lipid-coated mesoporous silica nanoparticle(MSNs@Lipo)for the co-delivery of TLR7/8 agonist resiquimod(R848)and TLR9 agonist CpG oligodeoxynucleotides(ODNs)(CpG@MSNs-R@L-M).R848 was firstly conjugated onto the nanoparticle via silane chemistry,which is acidic responsive drug release.Then,CpG was loaded onto the nanoparticle through the positive charge mainly from TLR7/8 agonist R848.Our in vitro experiments further indicated that both drugs have acid-responsive release properties and could be taken up by DCs and located on the endosomes of APCs.More importantly,CpG@MSNs-R@L-M could significantly improve the antitumor efficacy in B16F10 melanoma model.The mechanistic study demonstrated that CpG@MSNsR@L-M could remarkably modulate the TIME by promoting the maturation of DCs and repolarizing macrophages from M2 to M1 phenotype and facilitating the infiltration of tumor cytotoxic T cells.It was concluded that in comparison to single agonist,the codelivery of dual agonists,CpG and R848,can improve anti-tumor immune responses for cancer immunotherapy.

Community structure and activity potentials of archaeal communities in hadal sediments of the Mariana and Mussau trenches

Hadal trenches are the least explored marine habitat on earth. Archaea has been shown to be the dominant group in trench sediments. However, the activity potentials and detailed diversity of these communities as well as their inter-trench variations are still not known. In this study, we combined datasets from two pairs of primers to investigate at high resolution the structure and activity potentials of the archaeal communities in vertically sectioned sediment cores taken from the deepest points of the Mariana (10,853 m) and Mussau (7011 m) trenches. The compositions of the potentially active communities revealed, via 16S ribosomal RNA gene (rDNA) and RNA (rRNA), significant differences between samples. Marine Group I (MGI), with nine identified subgroups, was the most dominant class in the active archaeal communities of the two trenches. Significantly different species composition and vertical variations were observed between the two trenches. Vertical transitions from aerobic MGI α to anaerobic MGI η and υ subgroups were observed in MST but not in MT sediments, which might be related to the faster microbial oxygen consumption in MST. These results provide a better understanding on archaeal activity and diversity in trench sediments.