Junctional adhesion molecule-like protein as a novel target for kaempferol to ameliorate lung adenocarcinoma

Objective:Although there have been improvements in targeted therapy and immunotherapy,the majority of lung adenocarcinoma(LUAD)patients still lack effective therapies.Consequently,it is urgent to screen for new diagnosis biomarkers and pharmacological targets.Junctional adhesion molecule-like protein(JAML)was considered to be an oncogenic protein and may be a novel therapeutic target in LUAD.Kaempferol is a natural flavonoid that exhibits antitumor activities in LUAD.However,the effect of kaempferol on JAML is still unknown.Methods:Small interfering RNA was used to knockdown JAML expression.The cell viability was determined using the cell counting kit-8 assay.The proliferation of LUAD cells was evaluated using the 5-ethynyl-2'-deoxyuridine incorporation assay.The migration and invasion of LUAD cells were evaluated by transwell assays.Molecular mechanisms were explored by Western blotting.Results:JAML knockdown suppressed proliferation,migration and invasion of LUAD cells,and JAML deficiency restrained epithelial-mesenchymal transition(EMT)via inactivating the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)pathway.Using a PI3K activator(740Y-P),rescue experiments showed that phenotypes to JAML knockdown in LUAD cells were dependent on the PI3K/AKT/mTOR pathway.Kaempferol also inhibited proliferation,migration and invasion of A549 and H1299 cells and partially suppressed EMT through the PI3K/AKT/mTOR pathway.Knockdown of JAML ameliorated the inhibitory effect of kaempferol on LUAD cells.Kaempferol exerted anticancer effects by targeting JAML.Conclusion:JAML is a novel target for kaempferol against LUAD cells.

Overcoming bacterial physical defenses with molecule-like ultrasmall antimicrobial gold nanoclusters

The size of metal nanoparticles(NPs)is crucial in their biomedical applications.Although abundant studies on the size effects of metal NPs in the range of 2-100 nm have been conducted,the exploration of the ultrasmall metal nanoclusters(NCs)of~1 nm in size with unique features is quite limited.We synthesize three different sized gold(Au)NCs of different Au atom numbers and two bigger sized Au NPs protected by the same ligand to study the size influence on antimicrobial efficacy.The ultrasmall Au NCs can easily traverse the cell wall pores to be internalized inside bacteria,inducing reactive oxygen species generation to oxidize bacterial membrane and disturb bacterial metabolism.This explains why the Au NCs are antimicrobial while the Au NPs are non-antimicrobial,suggesting the key role of size in antimicrobial ability.Moreover,in contrast to the widely known size-dependent antimicrobial properties,the Au NCs of different atom numbers demonstrate molecule-like instead of size-dependent antimicrobial behavior with comparable effectiveness,indicating the unique molecule-like feature of ultrasmall Au NCs.Overcoming the bacterial defenses at the wall with ultrasmall Au NCs changes what was previously believed to harmless to the bacteria instead to a highly potent agent against the bacteria.

Critical behavior of a dynamical percolation model

The critical behavior of the dynamical percolation model,which realizes the molecular-aggregation conception and describes the crossover between the hadronic phase and the partonic phase,is studied in detail. The critical percolation distance for this model is obtained by using the probability P∞ of the appearance of an infinite cluster. Utilizing the finite-size scaling method the critical exponents γ/ν and τ are extracted from the distribution of the average cluster size and cluster number density. The influences of two model related factors,i.e. the maximum bond number and the definition of the infinite cluster,on the critical behavior are found to be small.